Nucleic acid and corresponding protein entitled 151P3D4 useful in treatment and detection of cancer

ABSTRACT

A novel gene (designated 151P3D4) and its encoded protein, and variants thereof, are described wherein 151P3D4 exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in the cancers listed in Table I. Consequently, 151P3D4 provides a diagnostic, prognostic, prophylactic and/or therapeutic target for cancer. The 151P3D4 gene or fragment thereof, or its encoded protein, or variants thereof, or a fragment thereof, can be used to elicit a humoral or cellular immune response; antibodies or T cells reactive with 151P3D4 can be used in active or passive immunization.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority from U.S. Serial No. 60/282,739filed Apr. 10, 2001, and U.S. Serial No. 60/286,630, filed Apr. 25,2001. The contents of these applications are hereby incorporated byreference herein in their entirety.

STATEMENT OF RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSOREDRESEARCH

[0002] Not applicable.

FIELD OF THE INVENTION

[0003] The invention described herein relates to a gene and its encodedprotein, termed 151P3D4, expressed in certain cancers, and to diagnosticand therapeutic methods and compositions useful in the management ofcancers that express 151P3D4.

BACKGROUND OF THE INVENTION

[0004] Cancer is the second leading cause of human death next tocoronary disease. Worldwide, millions of people die from cancer everyyear. In the United States alone, as reported by the American CancerSociety, cancer causes the death of well over a half-million peopleannually, with over 1.2 million new cases diagnosed per year. Whiledeaths from heart disease have been declining significantly, thoseresulting from cancer generally are on the rise. In the early part ofthe next century, cancer is predicted to become the leading cause ofdeath.

[0005] Worldwide, several cancers stand out as the leading killers. Inparticular, carcinomas of the lung, prostate, breast, colon, pancreas,and ovary represent the primary causes of cancer death. These andvirtually all other carcinomas share a common lethal feature. With veryfew exceptions, metastatic disease from a carcinoma is fatal. Moreover,even for those cancer patients who initially survive their primarycancers, common experience has shown that their lives are dramaticallyaltered. Many cancer patients experience strong anxieties driven by theawareness of the potential for recurrence or treatment failure. Manycancer patients experience physical debilitations following treatment.Furthermore, many cancer patients experience a recurrence.

[0006] Worldwide, prostate cancer is the fourth most prevalent cancer inmen. In North America and Northern Europe, it is by far the most commoncancer in males and is the second leading cause of cancer death in men.In the United States alone, well over 30,000 men die annually of thisdisease-second only to lung cancer. Despite the magnitude of thesefigures, there is still no effective treatment for metastatic prostatecancer. Surgical prostatectomy, radiation therapy, hormone ablationtherapy, surgical castration and chemotherapy continue to be the maintreatment modalities. Unfortunately, these treatments are ineffectivefor many and are often associated with undesirable consequences.

[0007] On the diagnostic front, the lack of a prostate tumor marker thatcan accurately detect early-stage, localized tumors remains asignificant limitation in the diagnosis and management of this disease.Although the serum prostate specific antigen (PSA) assay has been a veryuseful tool, however its specificity and general utility is widelyregarded as lacking in several important respects.

[0008] Progress in identifying additional specific markers for prostatecancer has been improved by the generation of prostate cancer xenograftsthat can recapitulate different stages of the disease in mice. The LAPC(Los Angeles Prostate Cancer) xenografts are prostate cancer xenograftsthat have survived passage in severe combined immune deficient (SCID)mice and have exhibited the capacity to mimic the transition fromandrogen dependence to androgen independence (Klein et al., 1997, Nat.Med. 3:402). More recently identified prostate cancer markers includePCTA-1 (Su et al., 1996, Proc. Natl. Acad. Sci. USA 93: 7252),prostate-specific membrane (PSM) antigen (Pinto et al., Clin Cancer ResSep. 2, 1996 (9): 1445-51), STEAP (Hubert, et al., Proc Natl Acad SciUSA. Dec. 7, 1999; 96(25): 14523-8) and prostate stem cell antigen(PSCA) (Reiter et al., 1998, Proc. Natl. Acad. Sci. USA 95: 1735).

[0009] While previously identified markers such as PSA, PSM, PCTA andPSCA have facilitated efforts to diagnose and treat prostate cancer,there is need for the identification of additional markers andtherapeutic targets for prostate and related cancers in order to furtherimprove diagnosis and therapy.

[0010] Renal cell carcinoma (RCC) accounts for approximately 3 percentof adult malignancies. Once adenomas reach a diameter of 2 to 3 cm,malignant potential exists. In the adult, the two principal malignantrenal tumors are renal cell adenocarcinoma and transitional cellcarcinoma of the renal pelvis or ureter. The incidence of renal celladenocarcinoma is estimated at more than 29,000 cases in the UnitedStates, and more than 11,600 patients died of this disease in 1998.Transitional cell carcinoma is less frequent, with an incidence ofapproximately 500 cases per year in the United States.

[0011] Surgery has been the primary therapy for renal celladenocarcinoma for many decades. Until recently, metastatic disease hasbeen refractory to any systemic therapy. With recent developments insystemic therapies, particularly immunotherapies, metastatic renal cellcarcinoma may be approached aggressively in appropriate patients with apossibility of durable responses. Nevertheless, there is a remainingneed for effective therapies for these patients.

[0012] Of all new cases of cancer in the United States, bladder cancerrepresents approximately 5 percent in men (fifth most common neoplasm)and 3 percent in women (eighth most common neoplasm). The incidence isincreasing slowly, concurrent with an increasing older population. In1998, there was an estimated 54,500 cases, including 39,500 in men and15,000 in women. The age-adjusted incidence in the United States is 32per 100,000 for men and 8 per 100,000 in women. The historic male/femaleratio of 3:1 may be decreasing related to smoking patterns in women.There were an estimated 11,000 deaths from bladder cancer in 1998 (7,800in men and 3,900 in women). Bladder cancer incidence and mortalitystrongly increase with age and will be an increasing problem as thepopulation becomes more elderly.

[0013] Most bladder cancers recur in the bladder. Bladder cancer ismanaged with a combination of transurethral resection of the bladder(TUR) and intravesical chemotherapy or immunotherapy. The multifocal andrecurrent nature of bladder cancer points out the limitations of TUR.Most muscle-invasive cancers are not cured by TUR alone. Radicalcystectomy and urinary diversion is the most effective means toeliminate the cancer but carry an undeniable impact on urinary andsexual function. There continues to be a significant need for treatmentmodalities that are beneficial for bladder cancer patients.

[0014] An estimated 130,200 cases of colorectal cancer occurred in 2000in the United States, including 93,800 cases of colon cancer and 36,400of rectal cancer. Colorectal cancers are the third most common cancersin men and women. Incidence rates declined significantly during1992-1996 (−2.1% per year). Research suggests that these declines havebeen due to increased screening and polyp removal, preventingprogression of polyps to invasive cancers. There were an estimated56,300 deaths (47,700 from colon cancer, 8,600 from rectal cancer) in2000, accounting for about 11% of all U.S. cancer deaths.

[0015] At present, surgery is the most common form of therapy forcolorectal cancer, and for cancers that have not spread, it isfrequently curative. Chemotherapy, or chemotherapy plus radiation, isgiven before or after surgery to most patients whose cancer has deeplyperforated the bowel wall or has spread to the lymph nodes. A permanentcolostomy (creation of an abdominal opening for elimination of bodywastes) is occasionally needed for colon cancer and is infrequentlyrequired for rectal cancer. There continues to be a need for effectivediagnostic and treatment modalities for colorectal cancer.

[0016] There were an estimated 164,100 new cases of lung and bronchialcancer in 2000, accounting for 14% of all U.S. cancer diagnoses. Theincidence rate of lung and bronchial cancer is declining significantlyin men, from a high of 86.5 per 100,000 in 1984 to 70.0 in 1996. In the1990s, the rate of increase among women began to slow. In 1996, theincidence rate in women was 42.3 per 100,000.

[0017] Lung and bronchial cancer caused an estimated 156,900 deaths in2000, accounting for 28% of all cancer deaths. During 1992-1996,mortality from lung cancer declined significantly among men (−1.7% peryear) while rates for women were still significantly increasing (0.9%per year). Since 1987, more women have died each year of lung cancerthan breast cancer, which, for over 40 years, was the major cause ofcancer death in women. Decreasing lung cancer incidence and mortalityrates most likely resulted from decreased smoking rates over theprevious 30 years; however, decreasing smoking patterns among women lagbehind those of men. Of concern, although the declines in adult tobaccouse have slowed, tobacco use in youth is increasing again.

[0018] Treatment options for lung and bronchial cancer are determined bythe type and stage of the cancer and include surgery, radiation therapy,and chemotherapy. For many localized cancers, surgery is usually thetreatment of choice. Because the disease has usually spread by the timeit is discovered, radiation therapy and chemotherapy are often needed incombination with surgery. Chemotherapy alone or combined with radiationis the treatment of choice for small cell lung cancer; on this regimen,a large percentage of patients experience remission, which in some casesis long lasting. There is however, an ongoing need for effectivetreatment and diagnostic approaches for lung and bronchial cancers.

[0019] An estimated 182,800 new invasive cases of breast cancer wereexpected to occur among women in the United States during 2000.Additionally, about 1,400 new cases of breast cancer were expected to bediagnosed in men in 2000. After increasing about 4% per year in the1980s, breast cancer incidence rates in women have leveled off in the1990s to about 110.6 cases per 100,000.

[0020] In the United States alone, there were an estimated 41,200 deaths(40,800 women, 400 men) in 2000 due to breast cancer. Breast cancerranks second among cancer deaths in women. According to the most recentdata, mortality rates declined significantly during 1992-1996 with thelargest decreases in younger women, both white and black. Thesedecreases were probably the result of earlier detection and improvedtreatment.

[0021] Taking into account the medical circumstances and the patient'spreferences, treatment of breast cancer may involve lumpectomy (localremoval of the tumor) and removal of the lymph nodes under the arm;mastectomy (surgical removal of the breast) and removal of the lymphnodes under the arm; radiation therapy; chemotherapy; or hormonetherapy. Often, two or more methods are used in combination. Numerousstudies have shown that, for early stage disease, long-term survivalrates after lumpectomy plus radiotherapy are similar to survival ratesafter modified radical mastectomy. Significant advances inreconstruction techniques provide several options for breastreconstruction after mastectomy. Recently, such reconstruction has beendone at the same time as the mastectomy.

[0022] Local excision of ductal carcinoma in situ (DCIS) with adequateamounts of surrounding normal breast tissue may prevent the localrecurrence of the DCIS. Radiation to the breast and/or tamoxifen mayreduce the chance of DCIS occurring in the remaining breast tissue. Thisis important because DCIS, if left untreated, may develop into invasivebreast cancer. Nevertheless, there are serious side effects or sequelaeto. these treatments. There is, therefore, a need for efficacious breastcancer treatments.

[0023] There were an estimated 23,100 new cases of ovarian cancer in theUnited States in 2000. It accounts for 4% of all cancers among women andranks second among gynecologic cancers. During 1992-1996, ovarian cancerincidence rates were significantly declining. Consequent to ovariancancer, there were an estimated 14,000 deaths in 2000. Ovarian cancercauses more deaths than any other cancer of the female reproductivesystem.

[0024] Surgery, radiation therapy, and chemotherapy are treatmentoptions for ovarian cancer. Surgery usually includes the removal of oneor both ovaries, the fallopian tubes (salpingo-oophorectomy), and theuterus (hysterectomy). In some very early tumors, only the involvedovary will be removed, especially in young women who wish to havechildren. In advanced disease, an attempt is made to remove allintra-abdominal disease to enhance the effect of chemotherapy. Therecontinues to be an important need for effective treatment options forovarian cancer.

[0025] There were an estimated 28,300 new cases of pancreatic cancer inthe United States in 2000. Over the past 20 years, rates of pancreaticcancer have declined in men. Rates among women have remainedapproximately constant but may be beginning to decline. Pancreaticcancer caused an estimated 28,200 deaths in 2000 in the United States.Over the past 20 years, there has been a slight but significant decreasein mortality rates among men (about −0.9% per year) while rates haveincreased slightly among women.

[0026] Surgery, radiation therapy, and chemotherapy are treatmentoptions for pancreatic cancer. These treatment options can extendsurvival and/or relieve symptoms in many patients but are not likely toproduce a cure for most. There is a significant need for additionaltherapeutic and diagnostic options for pancreatic cancer.

SUMMARY OF THE INVENTION

[0027] The present invention relates to a gene, designated 151P3D4, thathas now been found to be over-expressed in the cancer(s) listed in TableI. Northern blot expression analysis of 151P3D4 gene expression innormal tissues shows a restricted expression pattern in adult tissues.The nucleotide (FIG. 2) and amino acid (FIG. 2, and FIG. 3) sequences of151P3D4 are provided. The tissue-related profile of 151P3D4 in normaladult tissues, combined with the over-expression observed in the tissueslisted in Table I, shows that 151P3D4 is aberrantly over-expressed in atleast some cancers, and thus serves as a useful diagnostic,prophylactic, prognostic, and/or therapeutic target for cancers of thetissue(s) such as those listed in Table I.

[0028] The invention provides polynucleotides corresponding orcomplementary to all or part of the 151P3D4 genes, mRNAs, and/or codingsequences, preferably in isolated form, including polynucleotidesencoding 151P3D4-related proteins and fragments of 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or more than25 contiguous amino acids; at least 30, 35, 40, 45, 50, 55, 60, 65, 70,80, 85, 90, 95, 100 or more than 100 contiguous amino acids of a151P3D4-related protein, as well as the peptides/proteins themselves;DNA, RNA, DNA/RNA hybrids, and related molecules, polynucleotides oroligonucleotides complementary or having at least a 90% homology to the151P3D4 genes or mRNA sequences or parts thereof, and polynucleotides oroligonucleotides that hybridize to the 151P3D4 genes, mRNAs, or to151P3D4-encoding polynucleotides. Also provided are means for isolatingcDNAs and the genes encoding 151P3D4. Recombinant DNA moleculescontaining 151P3D4 polynucleotides, cells transformed or transduced withsuch molecules, and host-vector systems for the expression of 151P3D4gene products are also provided. The invention further providesantibodies that bind to 151P3D4 proteins and polypeptide fragmentsthereof, including polyclonal and monoclonal antibodies, murine andother mammalian antibodies, chimeric antibodies, humanized and fullyhuman antibodies, and antibodies labeled with a detectable marker ortherapeutic agent. In certain embodiments there is a proviso that theentire nucleic acid sequence of FIG. 2 is not encoded and/or the entireamino acid sequence of FIG. 2 is not prepared. In certain embodiments,the entire nucleic acid sequence of FIG. 2 is encoded and/or the entireamino acid sequence of FIG. 2 is prepared, either of which are inrespective human unit dose forms.

[0029] The invention further provides methods for detecting the presenceand status of 151P3D4 polynucleotides and proteins in various biologicalsamples, as well as methods for identifying cells that express 151P3D4.A typical embodiment of this invention provides methods for monitoring151P3D4 gene products in a tissue or hematology sample having orsuspected of having some form of growth dysregulation such as cancer.

[0030] The invention further provides various immunogenic or therapeuticcompositions and strategies for treating cancers that express 151P3D4such as cancers of tissues listed in Table I, including therapies aimedat inhibiting the transcription, translation, processing or function of151P3D4 as well as cancer vaccines. In one aspect, the inventionprovides compositions, and methods comprising them, for treating acancer that expresses 151P3D4 in a human subject wherein the compositioncomprises a carrier suitable for human use and a human unit dose of oneor more than one agent that inhibits the production or function of151P3D4. Preferably, the carrier is a uniquely human carrier. In anotheraspect of the invention, the agent is a moiety that is immunoreactivewith 151P3D4 protein. Non-limiting examples of such moieties include,but are not limited to, antibodies (such as single chain, monoclonal,polyclonal, humanized, chimeric, or human antibodies), functionalequivalents thereof (whether naturally occurring or synthetic), andcombinations thereof. The antibodies can be conjugated to a diagnosticor therapeutic moiety. In another aspect, the agent is a small moleculeas defined herein.

[0031] In another aspect, the agent comprises one or more than onepeptide which comprises a cytotoxic T lymphocyte (CTL) epitope thatbinds an HLA class I molecule in a human to elicit a CTL response to151P3D4 and/or one or more than one peptide which comprises a helper Tlymphocyte (HTL) epitope which binds an HLA class II molecule in a humanto elicit an HTL response. The peptides of the invention may be on thesame or on one or more separate polypeptide molecules. In a furtheraspect of the invention, the agent comprises one or more than onenucleic acid molecule that expresses one or more than one of the CTL orHTL response stimulating peptides as described above. In yet anotheraspect of the invention, the one or more than one nucleic acid moleculemay express a moiety that is immunologically reactive with 151P3D4 asdescribed above. The one or more than one nucleic acid molecule may alsobe, or encodes, a molecule that inhibits production of 151P3D4.Non-limiting examples of such molecules include, but are not limited to,those complementary to a nucleotide sequence essential for production of151P3D4 (e.g. antisense sequences or molecules that form a triple helixwith a nucleotide double helix essential for 151P3D4 production) or aribozyme effective to lyse 151P3D4 mRNA.

[0032] Another embodiment of the invention is antibody epitopes whichcomprise a peptide regions, or an oligonucleotide encoding the peptideregion, that has one two, three, four, or five of the followingcharacteristics:

[0033] i) a peptide region of at least 5 amino acids of a particularpeptide of FIG. 3, in any whole number increment up to the full lengthof that protein in FIG. 3, that includes an amino acid position having avalue equal to or greater than 0.5, 0.6, 0.7, 0.8, 0.9, or having avalue equal to 1.0, in the Hydrophilicity profile of FIG. 5;

[0034] ii) a peptide region of at least 5 amino acids of a particularpeptide of FIG. 3, in any whole number increment up to the full lengthof that protein in FIG. 3, that includes an amino acid position having avalue equal to or less than 0.5, 0.4, 0.3, 0.2, 0.1, or having a valueequal to 0.0, in the Hydropathicity profile of FIG. 6;

[0035] iii) a peptide region of at least 5 amino acids of a particularpeptide of FIG. 3, in any whole number increment up to the full lengthof that protein in FIG. 3, that includes an amino acid position having avalue equal to or greater than 0.5, 0.6, 0.7, 0.8, 0.9, or having avalue equal to 1.0, in the Percent Accessible Residues profile of FIG.7;

[0036] iv) a peptide region of at least 5 amino acids of a particularpeptide of FIG. 3, in any whole number increment up to the full lengthof that protein in FIG. 3, that includes an amino acid position having avalue equal to or greater than 0.5, 0.6, 0.7, 0.8, 0.9, or having avalue equal to 1.0, in the Average Flexibility profile of FIG. 8; or

[0037] v) a peptide region of at least 5 amino acids of a particularpeptide of FIG. 3, in any whole number increment up to the full lengthof that protein in FIG. 3, that includes an amino acid position having avalue equal to or greater than 0.5, 0.6, 0.7, 0.8, 0.9, or having avalue equal to 1.0, in the Beta-turn profile of FIG. 9.

BRIEF DESCRIPTION OF THE FIGURES

[0038]FIG. 1. The 151P3D4 SSH sequence of 417 nucleotides.

[0039]FIG. 2. The cDNA (SEQ ID. NO.:______) and amino acid sequence (SEQID. NO.:______) of 151P3D4 v.1 clone 1-placenta (also called “151P3D4v.1” or “151P3D4 variant 1”) is shown in FIG. 2A. The start methionineis underlined. The open reading frame extends from nucleic acid 316-1380including the stop codon. The cDNA (SEQ ID. NO.:______) and amino acidsequence (SEQ ID. NO.:______) of 151P3D4 variant 2 (also called “151P3D4v.2”) is shown in FIG. 2B. The codon for the start methionine isunderlined. The open reading frame extends from nucleic acid 1-2166including the stop codon. The cDNA (SEQ ID. NO.:______) and amino acidsequence (SEQ ID. NO.:______) of 151P3D4 variant 3 (also called “151P3D4v.3”) is shown in FIG. 2C. The codon for the start methionine isunderlined. The open reading frame extends from nucleic acid 316-1380including the stop codon. The cDNA (SEQ ID. NO.:______) and amino acidsequence (SEQ ID. NO.:______) of 151P3D4 variant 4 (also called “151P3D4v.4”) is shown in FIG. 2D. The codon for the start methionine isunderlined. The open reading frame extends from nucleic acid 316-1380including the stop codon. The cDNA (SEQ ID. NO.:______) and amino acidsequence (SEQ ID. NO.:______) of 151P3D4 variant 5 (also called “151P3D4v.5”) is shown in FIG. 2E. The codon for the start methionine isunderlined. The open reading frame extends from nucleic acid 316-1380including the stop codon. The cDNA (SEQ ID. NO.:______) and amino acidsequence (SEQ ID. NO.:______) of 151P3D4 variant 6 (also called “151P3D4v.6”) is shown in FIG. 2F. The codon for the start methionine isunderlined. The open reading frame extends from nucleic acid 316-1380including the stop codon. The cDNA (SEQ ID. NO.:______) and amino acidsequence (SEQ ID. NO.:______) of 151P3D4 variant 7 (also called “151P3D4v.7”) is shown in FIG. 2G. The codon for the start methionine isunderlined. The open reading frame extends from nucleic acid 316-1380including the stop codon. The cDNA (SEQ ID. NO.:______) and amino acidsequence (SEQ ID. NO.:______) of 151P3D4 variant 8 (also called “151P3D4v.8”) is shown in FIG. 2H. The codon for the start methionine isunderlined. The open reading frame extends from nucleic acid 316-1380including the stop codon. The cDNA (SEQ ID. NO.:______) and amino acidsequence (SEQ ID. NO.:______) of 151P3D4 variant 9 (also called “151P3D4v.9”) is shown in FIG. 2I. The codon for the start methionine isunderlined. The open reading frame extends from nucleic acid 316-1380including the stop codon. The cDNA (SEQ ID. NO.:______) and amino acidsequence (SEQ ID. NO.:______) of 151P3D4 variant 10 (also called“151P3D4 v.10”) is shown in FIG. 2J. The codon for the start methionineis underlined. The open reading frame extends from nucleic acid 316-1380including the stop codon. The cDNA (SEQ ID. NO.:______) and amino acidsequence (SEQ ID. NO.:______) of 151P3D4 variant 11 (also called“151P3D4 v.11”) is shown in FIG. 2K. The codon for the start methionineis underlined. The open reading frame extends from nucleic acid 316-1380including the stop codon. As used herein, a reference to 151P3D4includes all variants thereof, including those shown in FIGS. 10 and 12.

[0040]FIG. 3. Amino acid sequence of 151P3D4 v.1 (SEQ ID. NO.:______) isshown in FIG. 3A; it has 354 amino acids. The amino acid sequence of151P3D4 v.2 (SEQ ID. NO.:______) is shown in FIG. 3B; it has 721 aminoacids. As used herein, a reference to 151P3D4 includes all variantsthereof, including those shown in FIGS. 11 and 12.

[0041]FIG. 4. The nucleic acid sequence alignment of 151P3D4 v.1 withthe mRNA for human cartilage link protein is shown in FIG. 4A. The aminoacid sequence alignments of 151P3D4 v.1 with human cartilage linkprotein (4B), mouse cartilage link protein (4C), 151P3D4 v.2 (4D),hypothetical protein XP_(—)094318 (4E), bovine cartilage link protein(4F), and rat cartilage link protein (4G) are shown in FIGS. 4B-4G. Theamino acid sequence alignments of 151P3D4 v.2 with human cartilage linkprotein is shown in FIG. 4H. The clustal alignment of 151P3D4 v.1 and151P3D4 v.2 is shown in FIG. 4I.

[0042]FIG. 5. Hydrophilicity amino acid profile of A) 151P3D4 v.1 and B)151P3D4 v.2, determined by computer algorithm sequence analysis usingthe method of Hopp and Woods (Hopp T. P., Woods K. R., 1981. Proc. Natl.Acad. Sci. U.S.A. 78:3824-3828) accessed on the Protscale website(www.expasy.ch/cgi-bin/protscale.pl) through the ExPasy molecularbiology server.

[0043]FIG. 6. Hydropathicity amino acid profile of A) 151P3D4 v.1 and B)151P3D4 v.2, determined by computer algorithm sequence analysis usingthe method of Kyte and Doolittle (Kyte J., Doolittle R. F., 1982. J.Mol. Biol. 157:105-132) accessed on the ProtScale website(www.expasy.ch/cgi-bin/protscale.pl) through the ExPasy molecularbiology server.

[0044]FIG. 7. Percent accessible residues amino acid profile of A)151P3D4 v.1 and B) 151P3D4 v.2, determined by computer algorithmsequence analysis using the method of Janin (Janin J., 1979 Nature277:491-492) accessed on the ProtScale website(www.expasy.ch/cgi-bin/protscale.pl) through the ExPasy molecularbiology server.

[0045]FIG. 8. Average flexibility amino acid profile of A) 151P3D4 v.1and B) 151P3D4 v.2, determined by computer algorithm sequence analysisusing the method of Bhaskaran and Ponnuswamy (Bhaskaran R., andPonnuswamy P. K., 1988. Int. J. Pept. Protein Res. 32:242-255) accessedon the ProtScale website (www.expasy.ch/cgi-bin/protscale.pl) throughthe ExPasy molecular biology server.

[0046]FIG. 9. Beta-turn amino acid profile of A) 151P3D4 v.1 and B)151P3D4 v.2, determined by computer algorithm sequence analysis usingthe method of Deleage and Roux (Deleage, G., Roux B. 1987 ProteinEngineering 1:289-294) accessed on the ProtScale website(www.expasy.ch/cgi-bin/protscale.pl) through the ExPasy molecularbiology server.

[0047]FIG. 10. Schematic display of nucleotide variants of 151P3D4.Schematic alignment of Single Nucleotide Polymorphism(SNP) variants of151P3D4. Variants 151P3D4 v.3 through v.11are variants with singlenucleotide differences. Though these SNP variants are shown separately,they could also occur in any combinations and in any one of thetranscript variants that contains the base pairs. Numbers correspond tothose of 151P3D4 v.1. The black boxes show the same sequence as 151P3D4v.1 . SNPs are indicate the boxes.

[0048]FIG. 11. Schematic alignment of protein variants of 151P3D4.Nucleotide variants 151P3D4 v.2 through v.9 in FIG. 10 code for the sameprotein as 151P3D4 v.1. Variants 151P3D4 v.2 codes for a protein thatshares 321 aa with 151P3D4 v.1. Boxes with the same fill patternrepresent the same sequence. Numbers in “( )” underneath the boxescorrespond to 151P3D4 v.1.

[0049]FIG. 12. Schematic alignment of transcript variants of 151P3D4.Variant 151P3D4 v.2 is an alternative transcript, which shares the lastthree exons with 151P3D4 v.1. The first two exons of 151P3D4 v.1 arelocated in the sixth intron (between exons 6 and 7) of 151P3D4 v.2.Numbers in “( )” underneath the boxes correspond to those of 151P3D4v.2. Boxes with the same fill pattern represent the same sequence.

[0050]FIG. 13. Secondary structure prediction for 151P3D4 proteinvariants. The secondary structure of 151P3D4 protein variants 1 and 2(FIGS. A and B, respectively) were predicted using the HNN—HierarchicalNeural Network method (Guermeur, 1997,http://pbil.ibcp.fr/cgi-bin/npsa₁₃automat.pl?page=npsa_nn.html),accessed from the ExPasy molecular biology server(http://www.expasy.ch/tools/). This method predicts the presence andlocation of alpha helices, extended strands, and random coils from theprimary protein sequence. The percent of the protein in a givensecondary structure is also listed.

[0051]FIG. 14. Expression of 151P3D4 by RT-PCR. First strand cDNA wasprepared from vital pool 1 (liver, lung and kidney), vital pool 2(pancreas, colon and stomach), bladder cancer pool, kidney cancer pool,colon cancer pool, lung cancer pool, ovary cancer pool, breast cancerpool, and cancer metastasis pool. Normalization was performed by PCRusing primers to actin and GAPDH. Semi-quantitative PCR, using primersto 151P3D4, was performed at 26 and 30 cycles of amplification. Resultsshow strong expression of. 151P3D4 in ovary cancer pool. Expression of151P3D4 was also detected in bladder cancer pool, kidney cancer pool,colon cancer pool, lung cancer pool, breast cancer pool, cancermetastasis pool, vital pool 2, but not in vital pool 1.

[0052]FIG. 15. Expression of 151P3D4 in normal tissues. Two multipletissue northern blots (Clontech) both with 2 ug of mRNA/lane were probedwith the 151P3D4 sequence. Size standards in kilobases (kb) areindicated on the side. Results show expression of 151P3D4 in smallintestine and placenta. Lower level expression was also detected inheart and colon, but not in the other normal tissues tested.

[0053]FIG. 16. Expression of 151P3D4 in bladder cancer patient tissues.RNA was extracted from normal bladder (NB), bladder cancer cell lines(CL: UM-UC-3, J82, SCaBER), bladder cancer patient tumors (T) and normaladjacent tissue (NAT). Northern blots with 10 ug of total RNA wereprobed with the 151P3D4 SSH sequence. Size standards in kilobases areindicated on the side. Results show expression of 151P3D4 in patientbladder cancer tissues, and in UM-UC-3 bladder cancer cell lines, butnot in normal bladder nor in the other bladder cancer cell lines tested.

[0054]FIG. 17. Expression of 151P3D4 in kidney cancer patient tissues.RNA was extracted from kidney cancer cell lines (CL: 769-P, A498,SW839), normal kidney (NK), kidney cancer patient tumors (T) and theirnormal adjacent tissues (NAT). Northern blots with 10 ug of total RNAwere probed with the 151P3D4 SSH sequence. Size standards in kilobasesare on the side. Results show expression of 151P3D4 in patient kidneytumor tissues, but not in normal kidney, nor in the cell lines tested.

[0055]FIG. 18. Expression of 151P3D4 in ovary cancer patient tissues.RNA was extracted from ovary and cervical cancer cell lines (CL), normalovary (N), and ovary cancer patient tumor (T). Northern blots with 10 ugof total RNA were probed with the 151P3D4 SSH sequence. Size standardsin kilobases are on the side. Results show strong expression of 151P3D4in patient ovary cancer tissues, but not in normal ovary nor in theovary and cervical cancer cell lines.

[0056]FIG. 19. Expression of 151P3D4 in stomach and uterus human cancerspecimens. Expression of 151P3D4 was assayed in a panel of human stomachand uterus cancers (T) and their respective matched normal tissues (N)on RNA dot blots. 151P3D4 expression was seen in both stomach and uteruscancers.

[0057]FIG. 20. 151P3D4 expression in 293T cells following transfection.293T cells were transfected with either 151P3D4 .pcDNA3.1/mychis orpcDNA3.1/mychis vector control. Forty hours later, cell lysates werecollected. Samples were run on an SDS-PAGE acrylamide gel, blotted andstained with anti-his antibody. The blot was developed using the ECLchemiluminescence kit and visualized by autoradiography. Results showexpression of 151P3D4 from the 151P3D4. pcDNA3.1 /mychis mammalianexpression construct in the lysates of 151P3D4. pcDNA3.1/mychistransfected cells, but not from the control pcDNA3.1/mychis vector.

DETAILED DESCRIPTION OF THE INVENTION

[0058] Outline of Sections

[0059] I.) Definitions

[0060] II.) 151P3D4 Polynucleotides

[0061] II.A.) Uses of 151P3D4 Polynucleotides

[0062] II.A.1.) Monitoring of Genetic Abnormalities

[0063] II.A.2.) Antisense Embodiments

[0064] II.A.3.) Primers and Primer Pairs

[0065] II.A.4.) Isolation of 151P3D4-Encoding Nucleic Acid Molecules

[0066] II.A.5.) Recombinant Nucleic Acid Molecules and Host-VectorSystems

[0067] III.) 151P3D4-related Proteins

[0068] III.A.) Motif-bearing Protein Embodiments

[0069] III.B.) Expression of 151P3D4-related Proteins

[0070] III.C.) Modifications of 151P3D4-related Proteins

[0071] III.D.) Uses of 151P3D4-related Proteins

[0072] IV.) 151P3D4 Antibodies

[0073] V.) 151P3D4 Cellular Immune Responses

[0074] VI.) 151P3D4 Transgenic Animals

[0075] VII.) Methods for the Detection of 151P3D4

[0076] VIII.) Methods for Monitoring the Status of 151P3D4-related Genesand Their Products

[0077] IX.) Identification of Molecules That Interact With 151P3D4

[0078] X.) Therapeutic Methods and Compositions

[0079] X.A.) Anti-Cancer Vaccines

[0080] X.B.) 151P3D4 as a Target for Antibody-Based Therapy

[0081] X.C.) 151P3D4 as a Target for Cellular Immune Responses

[0082] X.C.1. Minigene Vaccines

[0083] X.C.2. Combinations of CTL Peptides with Helper Peptides

[0084] X.C.3. Combinations of CTL Peptides with T Cell Priming Agents

[0085] X.C.4. Vaccine Compositions Comprising DC Pulsed with CTL and/orHTL Peptides

[0086] X.D.) Adoptive Immunotherapy

[0087] X.E.) Administration of Vaccines for Therapeutic or ProphylacticPurposes

[0088] XI.) Diagnostic and Prognostic Embodiments of 151P3D4.

[0089] XII.) Inhibition of 151P3D4 Protein Function

[0090] XII.A.) Inhibition of 151P3D4 With Intracellular Antibodies

[0091] XII.B.) Inhibition of 151P3D4 with Recombinant Proteins

[0092] XII.C.) Inhibition of 151P3D4 Transcription or Translation

[0093] XII.D.) General Considerations for Therapeutic Strategies

[0094] XIII.) KITS

[0095] I.) Definitions:

[0096] Unless otherwise defined, all terms of art, notations and otherscientific terms or terminology used herein are intended to have themeanings commonly understood by those of skill in the art to which thisinvention pertains. In some cases, terms with commonly understoodmeanings are defined herein for clarity and/or for ready reference, andthe inclusion of such definitions herein should not necessarily beconstrued to represent a substantial difference over what is generallyunderstood in the art. Many of the techniques and procedures describedor referenced herein are well understood and commonly employed usingconventional methodology by those skilled in the art, such as, forexample, the widely utilized molecular cloning methodologies describedin Sambrook et al., Molecular Cloning: A Laboratory Manual 2nd. edition(1989) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. Asappropriate, procedures involving the use of commercially available kitsand reagents are generally carried out in accordance with manufacturerdefined protocols and/or parameters unless otherwise noted.

[0097] The terms “advanced prostate cancer”, “locally advanced prostatecancer”, “advanced disease” and “locally advanced disease” mean prostatecancers that have extended through the prostate capsule, and are meantto include stage C disease under the American Urological Association(AUA) system, stage C1-C2 disease under the Whitmore-Jewett systemn, andstage T3-T4 and N+ disease under the TNM (tumor, node, metastasis)system. In general surgery is not recommended for patients with locallyadvanced disease, and these patients have substantially less favorableoutcomes compared to patients having clinically localized(organ-confined) prostate cancer. Locally advanced disease is clinicallyidentified by palpable evidence of induration beyond the lateral borderof the prostate, or asymmetry or induration above the prostate base.Locally advanced prostate cancer is presently diagnosed pathologicallyfollowing radical prostatectomy if the tumor invades or penetrates theprostatic capsule, extends into the surgical margin, or invades theseminal vesicles.

[0098] “Altering the native glycosylation pattern” is intended forpurposes herein to mean deleting one or more carbohydrate moieties foundin native sequence 151P3D4 (either by removing the underlyingglycosylation site or by deleting the glycosylation by chemical and/orenzymatic means), and/or adding one or more glycosylation sites that arenot present in the native sequence 151P3D4. In addition, the phraseincludes qualitative changes in the glycosylation of the nativeproteins, involving a change in the nature and proportions of thevarious carbohydrate moieties present.

[0099] The term “analog” refers to a molecule which is structurallysimilar or shares similar or corresponding attributes with anothermolecule (e.g. a 151P3D4-related protein). For example an analog of a151P3D 4 protein can be specifically bound by an antibody or T cell thatspecifically binds to 151P3D4.

[0100] The term “antibody” is used in the broadest sense. Therefore an“antibody” can be naturally occurring or man-made such as monoclonalantibodies produced by conventional hybridoma technology. Anti-151P3D4antibodies comprise monoclonal and polyclonal antibodies as well asfragments containing the antigen-binding domain and/or one or morecomplementarity determining regions of these antibodies.

[0101] An “antibody fragment” is defined as at least a portion of thevariable region of the immunoglobulin molecule that binds to its target,i.e., the antigen-binding region. In one embodiment it specificallycovers single anti-151P3D4 antibodies and clones thereof (includingagonist, antagonist and neutralizing antibodies) and anti-151P3D4antibody compositions with polyepitopic specificity.

[0102] The term “codon optimized sequences” refers to nucleotidesequences that have been optimized for a particular host species byreplacing any codons having a usage frequency of less than about 20%.Nucleotide sequences that have been optimized for expression in a givenhost species by elimination of spurious polyadenylation sequences,elimination of exon/intron splicing signals, elimination oftransposon-like repeats and/or optimization of GC content in addition tocodon optimization are referred to herein as an “expression enhancedsequences.”

[0103] The term “cytotoxic agent” refers to a substance that inhibits orprevents the expression activity of cells, function of cells and/orcauses destruction of cells. The term is intended to include radioactiveisotopes chemotherapeutic agents, and toxins such as small moleculetoxins or enzymatically active toxins of bacterial, fungal, plant oranimal origin, including fragments and/or variants thereof. Examples ofcytotoxic agents include, but are not limited to maytansinoids, yttrium,bismuth, ricin, ricin A-chain, doxorubicin, daunorubicin, taxol,ethidium bromide, mitomycin, etoposide, tenoposide, vincristine,vinblastine, colchicine, dihydroxy anthracin dione, actinomycin,diphtheria toxin, Pseudomonas exotoxin (PE) A, PE40, abrin, abrin Achain, modeccin A chain, alpha-sarcin, gelonin, mitogellin,retstrictocin, phenomycin, enomycin, curicin, crotin, calicheamicin,sapaonaria officinalis inhibitor, and glucocorticoid and otherchemotherapeutic agents, as well as radioisotopes such as At²¹¹, I¹³¹,I¹²⁵, Y⁹⁰, Re¹⁸⁶, Re¹⁸⁸, Sm¹⁵³, Bi²¹², P³² and radioactive isotopes ofLu. Antibodies may also be conjugated to an anti-cancer pro-drugactivating enzyme capable of converting the pro-drug to its active form.

[0104] The term “homolog” refers to a molecule which exhibits homologyto another molecule, by for example, having sequences of chemicalresidues that are the same or similar at corresponding positions.

[0105] “Human Leukocyte Antigen” or “HLA” is a human class I or class IIMajor Histocompatibility Complex (MHC) protein (see, e.g., Stites, etal., IMMUNOLOGY, 8^(TH) Ed., Lange Publishing, Los Altos, Calif. (1994).

[0106] The terms “hybridize”, “hybridizing”, “hybridizes” and the like,used in the context of polynucleotides, are meant to refer toconventional hybridization conditions, preferably such as hybridizationin 50% formamide/6×SSC/0.1% SDS/100 μg/ml ssDNA, in which temperaturesfor hybridization are above 37 degrees C. and temperatures for washingin 0.1×SSC/0.1% SDS are above 55 degrees C.

[0107] The phrases “isolated” or “biologically pure” refer to materialwhich is substantially or essentially free from components whichnormally accompany the material as it is found in its native state.Thus, isolated peptides in accordance with the invention preferably donot contain materials normally associated with the peptides in their insitu environment. For example, a polynucleotide is said to be “isolated”when it is substantially separated from contaminant polynucleotides thatcorrespond or are complementary to genes other than the 151P3D4 genes orthat encode polypeptides other than 151P3D4 gene product or fragmentsthereof. A skilled artisan can readily employ nucleic acid isolationprocedures to obtain an isolated 151P3D4 polynucleotide. A protein issaid to be “isolated,” for example, when physical, mechanical orchemical methods are employed to remove the 151P3D4 proteins fromcellular constituents that are normally associated with the protein. Askilled artisan can readily employ standard purification methods toobtain an isolated l5IP3D4 protein. Alternatively, an isolated proteincan be prepared by chemical means.

[0108] The term “mammal” refers to any organism classified as a mammal,including mice, rats, rabbits, dogs, cats, cows, horses and humans. Inone embodiment of the invention, the mammal is a mouse. In anotherembodiment of the invention, the mammal is a human.

[0109] The terms “metastatic prostate cancer” and “metastatic disease”mean prostate cancers that have spread to regional lymph nodes or todistant sites, and are meant to include stage D disease under the AUAsystem and stage TxNxM+ under the TNM system. As is the case withlocally advanced prostate cancer, surgery is generally not indicated forpatients with metastatic disease, and hormonal (androgen ablation)therapy is a preferred treatment modality. Patients with metastaticprostate cancer eventually develop an androgen-refractory state within12 to 18 months of treatment initiation. Approximately half of theseandrogen-refractory patients die within 6 months after developing thatstatus. The most common site for prostate cancer metastasis is bone.Prostate cancer bone metastases are often osteoblastic rather thanosteolytic (i.e., resulting in net bone formation). Bone metastases arefound most frequently in the spine, followed by the femur, pelvis, ribcage, skull and humerus. Other common sites for metastasis include lymphnodes, lung, liver and brain. Metastatic prostate cancer is typicallydiagnosed by open or laparoscopic pelvic lymphadenectomy, whole bodyradionuclide scans, skeletal radiography, and/or bone lesion biopsy.

[0110] The term “monoclonal antibody” refers to an antibody obtainedfrom a population of substantially homogeneous antibodies, i.e., theantibodies comprising the population are identical except for possiblenaturally occurring mutations that are present in minor amounts.

[0111] A “motif”, as in biological motif of a 151P3D4-related protein,refers to any pattern of amino acids forming part of the primarysequence of a protein, that is associated with a particular function(e.g. protein-protein interaction, protein-DNA interaction, etc) ormodification (e.g. that is phosphorylated, glycosylated or amidated), orlocalization (e.g. secretory sequence, nuclear localization sequence,etc.) or a sequence that is correlated with being immunogenic, eitherhumorally or cellularly. A motif can be either contiguous or capable ofbeing aligned to certain positions that are generally correlated with acertain function or property. In the context of HLA motifs, “motif”refers to the pattern of residues in a peptide of defined length,usually a peptide of from about 8 to about 13 amino acids for a class IHLA motif and from about 6 to about 25 amino acids for a class II HLAmotif, which is recognized by a particular HLA molecule. Peptide motifsfor HLA binding are typically different for each protein encoded by eachhuman HLA allele and differ in the pattern of the primary and secondaryanchor residues.

[0112] A “pharmaceutical excipient” comprises a material such as anadjuvant, a carrier, pH-adjusting and buffering agents, tonicityadjusting agents, wetting agents, preservative, and the like.

[0113] “Pharmaceutically acceptable” refers to a non-toxic, inert,and/or composition that is physiologically compatible with humans orother mammals.

[0114] The term “polynucleotide” means a polymeric form of nucleotidesof at least 10 bases or base pairs in length, either ribonucleotides ordeoxynucleotides or a modified form of either type of nucleotide, and ismeant to include single and double stranded forms of DNA and/or RNA. Inthe art, this term if often used interchangeably with “oligonucleotide”.A polynucleotide can comprise a nucleotide sequence disclosed hereinwherein thymidine (T), as shown for example in FIG. 2, can also beuracil (U); this definition pertains to the differences between thechemical structures of DNA and RNA, in particular the observation thatone of the four major bases in RNA is uracil (U) instead of thymidine(T).

[0115] The term “polypeptide” means a polymer of at least about 4, 5, 6,7, or 8 amino acids. Throughout the specification, standard three letteror single letter designations for amino acids are used. In the art, thisterm is often used interchangeably with “peptide” or “protein”.

[0116] An HLA “primary anchor residue” is an amino acid at a specificposition along a peptide sequence which is understood to provide acontact point between the immunogenic peptide and the HLA molecule. Oneto three, usually two, primary anchor residues within a peptide ofdefined length generally defines a “motif” for an immunogenic peptide.These residues are understood to fit in close contact with peptidebinding groove of an HLA molecule, with their side chains buried inspecific pockets of the binding groove. In one embodiment, for example,the primary anchor residues for an HLA class I molecule are located atposition 2 (from the amino terminal position) and at the carboxylterminal position of a 8, 9, 10, 11, or 12 residue peptide epitope inaccordance with the invention. In another embodiment, for example, theprimary anchor residues of a peptide that will bind an HLA class IImolecule are spaced relative to each other, rather than to the terminiof a peptide, where the peptide is generally of at least 9 amino acidsin length. The primary anchor positions for each motif and supermotifare set forth in Table IV. For example, analog peptides can be createdby altering the presence or absence of particular residues in theprimary and/or secondary anchor positions shown in Table IV. Suchanalogs are used to modulate the binding affinity and/or populationcoverage of a peptide comprising a particular HLA motif or supermotif.

[0117] A “recombinant” DNA or RNA molecule is a DNA or RNA molecule thathas been subjected to molecular manipulation in vitro.

[0118] Non-limiting examples of small molecules include compounds thatbind or interact with 151P3D4, ligands including hormones,neuropeptides, chemokines, odorants, phospholipids, and functionalequivalents thereof that bind and preferably inhibit 151P3D4 proteinfunction. Such non-limiting small molecules preferably have a molecularweight of less than about 10 kDa, more preferably below about 9, about8, about 7, about 6, about 5 or about 4 kDa. In certain embodiments,small molecules physically associate with, or bind, 151P3D4 protein; arenot found in naturally occurring metabolic pathways; and/or are moresoluble in aqueous than non-aqueous solutions

[0119] “Stringency” of hybridization reactions is readily determinableby one of ordinary skill in the art, and generally is an empiricalcalculation dependent upon probe length, washing temperature, and saltconcentration. In general, longer probes require higher temperatures forproper annealing, while shorter probes need lower temperatures.Hybridization generally depends on the ability of denatured nucleic acidsequences to reanneal when complementary strands are present in anenvironment below their melting temperature. The higher the degree ofdesired homology between the probe and hybridizable sequence, the higherthe relative temperature that can be used. As a result, it follows thathigher relative temperatures would tend to make the reaction conditionsmore stringent, while lower temperatures less so. For additional detailsand explanation of stringency of hybridization reactions, see Ausubel etal., Current Protocols in Molecular Biology, Wiley IntersciencePublishers, (1995).

[0120] “Stringent conditions” or “high stringency conditions”, asdefined herein, are identified by, but not limited to, those that: (1)employ low ionic strength and high temperature for washing, for example0.015 M sodium chloride/0.0015 M sodium citrate/0.1% sodium dodecylsulfate at 50° C.; (2) employ during hybridization a denaturing agent,such as formamide, for example, 50% (v/v) formamide with 0.1% bovineserum albumin/0.1% Ficoll/0.1% polyvinylpyrrolidone/50 mM sodiumphosphate buffer at pH 6.5 with 750 mM sodium chloride, 75 mM sodiumcitrate at 42° C.; or (3) employ 50% formamide, 5×SSC (0.75 M NaCl,0.075 M sodium citrate), 50 mM sodium phosphate (pH 6.8), 0.1% sodiumpyrophosphate, 5× Denhardt's solution, sonicated salmon sperm DNA (50μg/ml), 0.1% SDS, and 10% dextran sulfate at 42° C., with washes at 42°C. in 0.2×SSC (sodium chloride/sodium. citrate) and 50% fornamide at 55°C., followed by a high-stringency wash consisting of 0.1×SSC containingEDTA at 55° C. “Moderately stringent conditions” are described by, butnot limited to, those in Sambrook et al., Molecular Cloning: ALaboratory Manual, New York: Cold Spring Harbor Press, 1989, and includethe use of washing solution and hybridization conditions (e.g.,temperature, ionic strength and % SDS) less stringent than thosedescribed above. An example of moderately stringent conditions isovernight incubation at 37° C. in a solution comprising: 20% formamide,5×SSC (150 mM NaCl, 15 mM trisodium citrate), 50 mM sodium phosphate (pH7.6), 5× Denhardt's solution, 10% dextran sulfate, and 20 mg/mLdenatured sheared salmon sperm DNA, followed by washing the filters in1×SSC at about 37-50° C. The skilled artisan will recognize how toadjust the temperature, ionic strength, etc. as necessary to accommodatefactors such as probe length and the like.

[0121] An HLA “supermotif” is a peptide binding specificity shared byHLA molecules encoded by two or more HLA alleles.

[0122] As used herein “to treat” or “therapeutic” and grammaticallyrelated terms, refer to any improvement of any consequence of disease,such as prolonged survival, less morbidity, and/or a lessening of sideeffects which are the byproducts of an alternative therapeutic modality;full eradication of disease is not required.

[0123] A “transgenic animal” (e.g., a mouse or rat) is an animal havingcells that contain a transgene, which transgene was introduced into theanimal or an ancestor of the animal at a prenatal, e.g., an embryonicstage. A “transgene” is a DNA that is integrated into the genome of acell from which a transgenic animal develops.

[0124] As used herein, an HLA or cellular immune response “vaccine” is acomposition that contains or encodes one or more peptides of theinvention. There are numerous embodiments of such vaccines, such as acocktail of one or more individual peptides; one or more peptides of theinvention comprised by a polyepitopic peptide; or nucleic acids thatencode such individual peptides or polypeptides, e.g., a minigene thatencodes a polyepitopic peptide. The “one or more peptides” can includeany whole unit integer from 1-150 or more, e.g., at least 2, 3, 4, 5, 6,7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43,44, 45, 46, 47, 48, 49, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100,105, 110, 115, 120, 125, 130, 135, 140, 145, or 150 or more peptides ofthe invention. The peptides or polypeptides can optionally be modified,such as by lipidation, addition of targeting or other sequences. HLAclass I peptides of the invention can be admixed with, or linked to, HLAclass II peptides, to facilitate activation of both cytotoxic Tlymphocytes and helper T lymphocytes. HLA vaccines can also comprisepeptide-pulsed antigen presenting cells, e.g., dendritic cells.

[0125] The term “variant” refers to a molecule that exhibits a variationfrom a described type or norm, such as a protein that has one or moredifferent amino acid residues in the corresponding position(s) of aspecifically described protein (e.g. the 151P3D4 protein shown in FIG. 2or FIG. 3. An analog is an example of a variant protein. Splice isoformsand single nucleotides polymorphisms (SNPs) are further examples ofvariants.

[0126] The “151P3D4-related proteins” of the invention include thosespecifically identified herein, as well as allelic variants,conservative substitution variants, analogs and homologs that can beisolated/generated and characterized without undue experimentationfollowing the methods outlined herein or readily available in the art.Fusion proteins that combine parts of different 151P3D4 proteins orfragments thereof, as well as fusion proteins of a 151P3D4 protein and aheterologous polypeptide are also included. Such 151P3D4 proteins arecollectively referred to as the 151P3D4-related proteins, the proteinsof the invention, or 151P3D4. The term “151P3D4-related protein” refersto a polypeptide fragment or a 151P3D4 protein sequence of 4, 5, 6, 7,8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, ormore than 25 amino acids; or, at least 30, 35, 40, 45, 50, 55, 60, 65,70, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145,150, 155, 160, 165, 170, 175, 180, 185, 190, 195, 200, 225, 250, 275,300, 325, 350, or 354 or more amino acids.

[0127] II.) 151P3D4 Polynucleotides

[0128] One aspect of the invention provides polynucleotidescorresponding or complementary to all or part of a 151P3D4 gene, mRNA,and/or coding sequence, preferably in isolated form, includingpolynucleotides encoding a 151P3D4-related protein and fragmentsthereof, DNA, RNA, DNA/RNA hybrid, and related molecules,polynucleotides or oligonucleotides complementary to a 151P3D4 gene ormRNA sequence or a part thereof, and polynucleotides or oligonucleotidesthat hybridize to a 151P3D4 gene, mRNA, or to a 151P3D4 encodingpolynucleotide (collectively, “151P3D4 polynucleotides”). In allinstances when referred to in this section, T can also be U in FIG. 2.

[0129] Embodiments of a 151P3D4 polynucleotide include: a 151P3D4polynucleotide having the sequence shown in FIG. 2, the nucleotidesequence of 151P3D4 as shown in FIG. 2 wherein T is U; at least 10contiguous nucleotides of a polynucleotide having the sequence as shownin FIG. 2; or, at least 10 contiguous nucleotides of a polynucleotidehaving the sequence as shown in FIG. 2 where T is U. For example,embodiments of 151P3D4 nucleotides comprise, without limitation:

[0130] (I) a polynucleotide comprising, consisting essentially of, orconsisting of a sequence as shown in FIG. 2 (SEQ ID NO:______), whereinT can also be U;

[0131] (II) a polynucleotide comprising, consisting essentially of, orconsisting of the sequence as shown in FIG. 2A (SEQ ID NO:______), fromnucleotide residue number 316 through nucleotide residue number 1380,including the stop codon, wherein T can also be U;

[0132] (III) a polynucleotide comprising, consisting essentially of, orconsisting of the sequence as shown in FIG. 2B (SEQ ID NO:______), fromnucleotide residue number 1 through nucleotide residue number 2166,including the stop codon, wherein T can also be U;

[0133] (IV) a polynucleotide comprising, consisting essentially of, orconsisting of the sequences as shown in FIGS. 2C-2K (SEQ ID NOs:______),from nucleotide residue number 316 through nucleotide residue number1380, including the a stop codon, wherein T can also be U;

[0134] (V) a polynucleotide that encodes a 151P3D4-related protein thatis at least 90% homologous to an entire amino acid sequence shown inFIGS. 2A-K (SEQ ID NO:______);

[0135] (VI) a polynucleotide that encodes a 151P3D4-related protein thatis at least 90% identical to an entire amino acid sequence shown inFIGS. 2A-K (SEQ ID NO:______);

[0136] (VII) a polynucleotide that encodes at least one peptide setforth in Tables V-XVIII and XXII-LI;

[0137] (VIII) a polynucleotide that encodes a peptide region of at least5 amino acids of a peptide of FIG. 3A in any whole number increment upto 354 that includes an amino acid position having a value greater than0.5 in the Hydrophilicity profile of FIG. 5A; or of FIG. 3B in any wholenumber increment up to 721 that includes an amino acid position having avalue greater than 0.5 in the Hydrophilicity profile of FIG. 5B;

[0138] (XIX) a polynucleotide that encodes a peptide region of at least5 amino acids of a peptide of FIG. 3A in any whole number increment upto 354 that includes an amino acid position having a value less than 0.5in the Hydropathicity profile of FIG. 6A; or of FIG. 3B in any wholenumber increment up to 721 that includes an amino acid position having avalue less than 0.5 in the Hydropathicity profile of FIG. 6B;

[0139] (X) a polynucleotide that encodes a peptide region of at least 5amino acids of a peptide of FIG. 3A in any whole number increment up to354 that includes an amino acid position having a value greater than 0.5in the Percent Accessible Residues profile of FIG. 7A; or of FIG. 3B inany whole number increment up to 721 that includes an amino acidposition having a value greater than 0.5 in the Percent AccessibleResidues profile of FIG. 7B;

[0140] (XII) a polynucleotide that encodes a peptide region of at least5 amino acids of a peptide of FIG. 3A in any whole number increment upto 354 that includes an amino acid position having a value greater than0.5 in the Average Flexibility profile of FIG. 8A; or of FIG. 3B in anywhole number increment up to 721 that includes an amino acid positionhaving a value greater than 0.5 in the Average Flexibility profile ofFIG. 8B;

[0141] (XIII) a polynucleotide that encodes a peptide region of at least5 amino acids of a peptide of FIG. 3A in any whole number increment upto 354 that includes an amino acid position having a value greater than0.5 in the Beta-turn profile of FIG. 9A; or of FIG. 3B in any wholenumber increment up to 721 that includes an amino acid position having avalue greater than 0.5 in the Beta-turn profile of FIG. 9B;

[0142] (XIV) a polynucleotide that is fully complementary to apolynucleotide of any one of (I)-(XIII).

[0143] (XV) a peptide that is encoded by any of (I)-(XIV); and

[0144] (XVI) a polynucleotide of any of (I)-(XIV) or peptide of (XV)together with a pharmaceutical excipient and/or in a human unit doseform.

[0145] As used herein, a range is understood to specifically discloseall whole unit positions thereof.

[0146] Typical embodiments of the invention disclosed herein include151P3D4 polynucleotides that encode specific portions of 151P3D4 mRNAsequences (and those which are complementary to such sequences) such asthose that encode the proteins and/or fragments thereof, for example:

[0147] (a) 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,21, 22, 23, 24, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90,95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160,165, 170, 175, 180, 185, 190, 195, 200, 225, 250, 275, 300, 325, 350, or354 or more contiguous amino acids of 151P3D4.

[0148] (b) 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,21, 22, 23, 24, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90,95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160,165, 170, 175, 180, 185, 190, 195, 200, 225, 250, 275, 300, 325, 350,375, 400, 425, 450, 475, 500, 525, 550, 575, 600, 625, 650, 675, 700, or721 or more contiguous amino acids of 151P3D4 variant 2.

[0149] For example, representative embodiments of the inventiondisclosed herein include: polynucleotides and their encoded peptidesthemselves encoding about amino acid 1 to about amino acid 10 of the151P3D4 protein shown in FIG. 2 or FIG. 3, polynucleotides encodingabout amino acid 10 to about amino acid 20 of the 151P3D4 protein shownin FIG. 2 or FIG. 3, polynucleotides encoding about amino acid 20 toabout amino acid 30 of the 151P3D4 protein shown in FIG. 2 or FIG. 3,polynucleotides encoding about amino acid 30 to about amino acid 40 ofthe 151P3D4 protein shown in FIG. 2 or FIG. 3, polynucleotides encodingabout amino acid 40 to about amino acid 50 of the 151P3D4 protein shownin FIG. 2 or FIG. 3, polynucleotides encoding about amino acid 50 toabout amino acid 60 of the 151P3D4 protein shown in FIG. 2 or FIG. 3,polynucleotides encoding about amino acid 60 to about amino acid 70 ofthe 151P3D4 protein shown in FIG. 2 or FIG. 3, polynucleotides encodingabout amino acid 70 to about amino acid 80 of the 151P3D4 protein shownin FIG. 2 or FIG. 3, polynucleotides encoding about amino acid 80 toabout amino acid 90 of the 151P3D4 protein shown in FIG. 2 or FIG. 3,polynucleotides encoding about amino acid 90 to about amino acid 100 ofthe 151P3D4 protein shown in FIG. 2 or FIG. 3, in increments of about 10amino acids, ending at the carboxyl terminal amino acid set forth inFIG. 2 or FIG. 3. Accordingly polynucleotides encoding portions of theamino acid sequence (of about 10 amino acids), of amino acids 100through the carboxyl terminal amino acid of the 151P3D4 protein areembodiments of the invention. Wherein it is understood that eachparticular amino acid position discloses that position plus or minusfive amino acid residues.

[0150] Polynucleotides encoding relatively long portions of a 151P3D4protein are also within the scope of the invention. For example,polynucleotides encoding from about amino acid 1 (or 20 or 30 or 40etc.) to about amino acid 20, (or 30, or 40 or 50 etc.) of the 151P3D4protein “or variant” shown in FIG. 2 or FIG. 3 can be generated by avariety of techniques well known in the art. These polynucleotidefragments can include any portion of the 151P3D4 sequence as shown inFIG. 2.

[0151] One embodiment of the invention comprises an HLA peptide, thatoccurs at least twice in Tables V-XVIII and XXII to LI collectively, oran oligonucleotide that encodes the HLA peptide. Another embodiment ofthe invention comprises an HLA peptide that occurs at least once inTables V-XVIII and at least once in tables XXII to LI, or anoligonucleotide that encodes the HLA peptide. In another embodiment ofthe invention, typical polynucleotide fragments can encode one or moreof the 151P3D4 protein or variant N-glycosylation sites, cAMP andcGMP-dependent protein kinase phosphorylation sites, casein kinase IIphosphorylation sites or N-myristoylation site and amidation sites.

[0152] II.A.) Uses of 151P3D4 Polynucleotides

[0153] II.A.1.) Monitoring of Genetic Abnormalities

[0154] The polynucleotides of the preceding paragraphs have a number ofdifferent specific uses. The human 151P3D4 gene maps to the chromosomallocation set forth in the Example entitled “Chromosomal Mapping of151P3D4.” For example, because the 151P3D4 gene maps to this chromosome,polynucleotides that encode different regions of the 151P3D4 proteinsare used to characterize cytogenetic abnormalities of this chromosomallocale, such as abnormalities that are identified as being associatedwith various cancers. In certain genes, a variety of chromosomalabnormalities including rearrangements have been identified as frequentcytogenetic abnormalities in a number of different cancers (see e.g.Krajinovic et al., Mutat. Res. 382(34): 81-83 (1998); Johansson et al.,Blood 86(10): 3905-3914 (1995) and Finger et al., P.N.A.S. 85(23):9158-9162 (1988)). Thus, polynucleotides encoding specific regions ofthe 151P3D4 proteins provide new tools that can be used to delineate;with greater precision than previously possible, cytogeneticabnormalities in the chromosomal region that encodes 151P3D4 that maycontribute to the malignant phenotype. In this context, thesepolynucleotides satisfy a need in the art for expanding the sensitivityof chromosomal screening in order to identify more subtle and lesscommon chromosomal abnormalities (see e.g. Evans et al, Am. J. Obstet.Gynecol 171(4): 1055-1057 (1994)).

[0155] Furthermore, as 151P3D4 was shown to be highly expressed inbladder and other cancers, 151P3D4 polynucleotides are used in methodsassessing the status of 151P3D4 gene products in normal versus canceroustissues. Typically, polynucleotides that encode specific regions of the151P3D4 proteins are used to assess the presence of perturbations (suchas deletions, insertions, point mutations, or alterations resulting in aloss of an antigen etc.) in specific regions of the 151P3D4 gene, suchas regions containing one or more motifs. Exemplary assays include bothRT-PCR assays as well as single-strand conformation polymorphism (SSCP)analysis (see, e.g., Marrogi et al., J. Cutan. Pathol. 26(8): 369-378(1999), both of which utilize polynucleotides encoding specific regionsof a protein to examine these regions within the protein.

[0156] II.A.2.) Antisense Embodiments

[0157] Other specifically contemplated nucleic acid related embodimentsof the invention disclosed herein are genomic DNA, cDNAs, rybozymes, andantisense molecules, as well as nucleic acid molecules based on analternative backbone, or including alternative bases, whether derivedfrom natural sources or synthesized, and include molecules capable ofinhibiting the RNA or protein expression of 151P3D4. For example,antisense molecules can be RNAs or other molecules, including peptidenucleic acids (PNAs) or non-nucleic acid molecules such asphosphorothioate derivatives, that specifically bind DNA or RNA in abase pair-dependent manner. A skilled artisan can readily obtain theseclasses of nucleic acid molecules using the 151P3D4 polynucleotides andpolynucleotide sequences disclosed herein.

[0158] Antisense technology entails the administration of exogenousoligonucleotides that bind to a target polynucleotide located within thecells. The term “antisense” refers to the fact that sucholigonucleotides are complementary to their intracellular targets, e.g.,151P3D4. See for example, Jack Cohen, Oligodeoxynucleotides, AntisenseInhibitors of Gene Expression, CRC Press, 1989; and Synthesis 1:1-5(1988). The 151P3D4 antisense oligonucleotides of the present inventioninclude derivatives such as S-oligonucleotides (phosphorothioatederivatives or S-oligos, see, Jack Cohen, supra), which exhibit enhancedcancer cell growth inhibitory action. S-oligos (nucleosidephosphorothioates) are isoelectronic analogs of an oligonucleotide(O-oligo) in which a nonbridging oxygen atom of the phosphate group isreplaced by a sulfur atom. The S-oligos of the present invention can beprepared by treatment of the corresponding O-oligos with3H-1,2-benzodithiol-3-one-1,1-dioxide, which is a sulfur transferreagent. See, e.g., Iyer, R. P. et al., J. Org. Chem. 55:4693-4698(1990); and Iyer, R. P. et al., J. Am. Chem. Soc. 112:1253-1254 (1990).Additional 151P3D4 antisense oligonucleotides of the present inventioninclude morpholino antisense oligonucleotides known in the art (see,e.g., Partridge et al., 1996, Antisense & Nucleic Acid Drug Development6: 169-175).

[0159] The 151P3D4 antisense oligonucleotides of the present inventiontypically can be RNA or DNA that is complementary to and stablyhybridizes with the first 100 5′ codons or last 100 3′ codons of a151P3D4 genomic sequence or the corresponding mRNA. Absolutecomplementarity is not required, although high degrees ofcomplementarity are preferred. Use of an oligonucleotide complementaryto this region allows for the selective hybridization to 151P3D4 mRNAand not to mRNA specifying other regulatory subunits of protein kinase.In one embodiment, 151P3D4 antisense oligonucleotides of the presentinvention are 15 to 30-mer fragments of the antisense DNA molecule thathave a sequence that hybridizes to 151P3D4 mRNA. Optionally, 151P3D4antisense oligonucleotide is a 30-mer oligonucleotide that iscomplementary to a region in the first 10 5′ codons or last 10 3′ codonsof 151P3D4. Alternatively, the antisense molecules are modified toemploy ribozymes in the inhibition of 151P3D4 expression, see, e.g., L.A. Couture & D. T. Stinchcomb; Trends Genet 12: 510-515 (1996).

[0160] II.A.3.) Primers and Primer Pairs

[0161] Further specific embodiments of this nucleotides of the inventioninclude primers and primer pairs, which allow the specific amplificationof polynucleotides of the invention or of any specific parts thereof,and probes that selectively or specifically hybridize to nucleic acidmolecules of the invention or to any part thereof. Probes can be labeledwith a detectable marker, such as, for example, a radioisotope,fluorescent compound, bioluminescent compound, a chemiluminescentcompound, metal chelator or enzyme. Such probes and primers are used todetect the presence of a 151P3D4 polynucleotide in a sample and as ameans for detecting a cell expressing a 151P3D4 protein.

[0162] Examples of such probes include polypeptides comprising all orpart of the human 151P3D4 cDNA sequence shown in FIG. 2. Examples ofprimer pairs capable of specifically amplifping 151P3D4 mRNAs are alsodescribed in the Examples. As will be understood by the skilled artisan,a great many different primers and probes can be prepared based on thesequences provided herein and used effectively to amplify and/or detecta 151P3D4 mRNA.

[0163] The 151P3D4 polynucleotides of the invention are useful for avariety of purposes, including but not limited to their use as probesand primers for the amplification and/or detection of the 151P3D4gene(s), mRNA(s), or fragments thereof; as reagents for the diagnosisand/or prognosis of prostate cancer and other cancers; as codingsequences capable of directing the expression of 151P3D4 polypeptides;as tools for modulating or inhibiting the expression of the 151P3D4gene(s) and/or translation of the 151P3D4 transcript(s); and astherapeutic agents.

[0164] The present invention includes the use of any probe as describedherein to identify and isolate a 151P3D4 or 151P3D4 related nucleic acidsequence from a naturally occurring source, such as humans or othermammals, as well as the isolated nucleic acid sequence per se, whichwould comprise all or most of the sequences found in the probe used.

[0165] II.A.4.) Isolation of 151P3D4-Encoding Nucleic Acid Molecules

[0166] The 151P3D4 cDNA sequences described herein enable the isolationof other polynucleotides encoding 151P3D4 gene product(s), as well asthe isolation of polynucleotides encoding 151P3D4 gene product homologsalternatively spliced isoforms, allelic variants, and mutant forms of a151P3D4 gene product as well as polynucleotides that encode analogs of151P3D4-related proteins. Various molecular cloning methods that can beemployed to isolate full length cDNAs encoding a 151P3D4 gene are wellknown (see, for example, Sambrook, J. et al., Molecular Cloning: ALaboratory Manual, 2d edition, Cold Spring Harbor Press, New York, 1989;Current Protocols in Molecular Biology. Ausubel et al, Eds., Wiley andSons, 1995). For example, lambda phage cloning methodologies can beconveniently employed, using commercially available cloning systems(e.g., Lambda ZAP Express, Stratagene). Phage clones containing 151P3D4gene cDNAs can be identified by probing with a labeled 151P3D4 cDNA or afragment thereof For example, in one embodiment, a 151P3D4 cDNA (e.g.,FIG. 2) or a portion thereof can be synthesized and used as a probe toretrieve overlapping and full-length cDNAs corresponding to a 151P3D4gene. A 151P3D4 gene itself can be isolated by screening genomic DNAlibraries, bacterial artificial chromosome libraries (BACs), yeastartificial chromosome libraries (YACs), and the like, with 151P3D4 DNAprobes or primers.

[0167] II.A.5.) Recombinant Nucleic Acid Molecules and Host-VectorSystems

[0168] The invention also provides recombinant DNA or RNA moleculescontaining a 151P3D4 polynucleotide, a fragment, analog or homologuethereof, including but not limited to phages, plasmids, phagemids,cosmids, YACs, BACs, as well as various viral and non-viral vectors wellknown in the art, and cells transformed or transfected with suchrecombinant DNA or RNA molecules. Methods for generating such moleculesare well known (see, for example, Sambrook et al., 1989, supra).

[0169] The invention further provides a host-vector system comprising arecombinant DNA molecule containing a 151P3D4 polynucleotide, fragment,analog or homologue thereof within a suitable prokaryotic or eukaryotichost cell. Examples of suitable eukaryotic host cells include a yeastcell, a plant cell, or an animal cell, such as a mammalian cell or aninsect cell (e.g., a baculovirus-infectible cell such as an Sf9 orHighFive cell). Examples of suitable mammalian cells include variousprostate cancer cell lines such as DU145 and TsuPr1, other transfectableor transducible prostate cancer cell lines, primary cells (PrEC), aswell as a number of mammalian cells routinely used for the expression ofrecombinant proteins (e.g., COS, CHO, 293, 293T cells). Moreparticularly, a polynucleotide comprising the coding sequence of 151P3D4or a fragment, analog or homolog thereof can be used to generate 151P3D4proteins or fragments thereof using any number of host-vector systemsroutinely used and widely known in the art.

[0170] A wide range of host-vector systems suitable for the expressionof 151P3D4 proteins or fragments thereof are available, see for example,Sambrook et al., 1989, supra; Current Protocols in Molecular Biology,1995, supra). Preferred vectors for mammalian expression include but arenot limited to pcDNA 3.1 myc-His-tag (Invitrogen) and the retroviralvector pSRAαtkneo (Muller et al., 1991, MCB 11:1785). Using theseexpression vectors, 151P3D4 can be expressed in several prostate cancerand non-prostate cell lines, including for example 293, 293T, rat-1, NIH3T3 and TsuPr1. The host-vector systems of the invention are useful forthe production of a 151P3D4 protein or fragment thereof. Suchhost-vector systems can be employed to study the functional propertiesof 151P3D4 and 151P3D4 mutations or analogs.

[0171] Recombinant human 151P3D4 protein or an analog or homolog orfragment thereof can be produced by mammalian cells transfected with aconstruct encoding a 151P3D4-related nucleotide. For example, 293T cellscan be transfected with an expression plasmid encoding 151P3D4 orfragment, analog or homolog thereof, a 151P3D4-related protein isexpressed in the 293T cells, and the recombinant 151P3D4 protein isisolated using standard purification methods (e.g., affinitypurification using anti-151P3D4 antibodies). In another embodiment, a151P3D4 coding sequence is subcloned into the retroviral vectorpSRαMSVtkneo and used to infect various mammalian cell lines, such asNIH 3T3, TsuPr1, 293 and rat-1 in order to establish 151P3D4 expressingcell lines. Various other expression systems well known in the art canalso be employed. Expression constructs encoding a leader peptide joinedin frame to a 151P3D4 coding sequence can be used for the generation ofa secreted form of recombinant 151P3D4 protein.

[0172] As discussed herein, redundancy in the genetic code permitsvariation in 151P3D4 gene sequences. In particular, it is known in theart that specific host species often have specific codon preferences,and thus one can adapt the disclosed sequence as preferred for a desiredhost. For example, preferred analog codon sequences typically have rarecodons (i.e., codons having a usage frequency of less than about 20% inknown sequences of the desired host) replaced with higher frequencycodons. Codon preferences for a specific species are calculated, forexample, by utilizing codon usage tables available on the INTERNET suchas at URL www.dna.affrc.go.jp/˜nakamura/codon.html.

[0173] Additional sequence modifications are known to enhance proteinexpression in a cellular host. These include elimination of sequencesencoding spurious polyadenylation signals, exon/intron splice sitesignals, transposon-like repeats, and/or other such well-characterizedsequences that are deleterious to gene expression. The GC content of thesequence is adjusted to levels average for a given cellular host, ascalculated by reference to known genes expressed in the host cell. Wherepossible, the sequence is modified to avoid predicted hairpin secondarymRNA structures. Other useful modifications include the addition of atranslational initiation consensus sequence at the start of the openreading frame, as described in Kozak, Mol. Cell Bio., 9:5073-5080(1989). Skilled artisans understand that the general rule thateukaryotic ribosomes initiate translation exclusively at the 5′ proximalAUG codon is abrogated only under rare conditions (see, e.g., Kozak PNAS92(7): 2662-2666, (1995) and Kozak NAR 15(20): 8125-8148 (1987)).

[0174] III.) 151P3D4Related Proteins

[0175] Another aspect of the present invention provides 151P3D4-relatedproteins. Specific embodiments of 151P3D4 proteins comprise apolypeptide having all or part of the amino acid sequence of human151P3D4 as shown in FIG. 2 or FIG. 3. Alternatively, embodiments of151P3D4 proteins comprise variant, homolog or analog polypeptides thathave alterations in the amino acid sequence of 151P3D4 shown in FIG. 2or FIG. 3.

[0176] In general, naturally occurring allelic variants of human 151P3D4share a high degree of structural identity and homology (e.g., 90% ormore homology). Typically, allelic variants of a 151P3D4 protein containconservative amino acid substitutions within the 151P3D4 sequencesdescribed herein or contain a substitution of an amino acid from acorresponding position in a homologue of 151P3D4. One class of 151P3D4allelic variants are proteins that share a high degree of homology withat least a small region of a particular 151P3D4 amino acid sequence, butfurther contain a radical departure from the sequence, such as anon-conservative substitution, truncation, insertion or frame shift. Incomparisons of protein sequences, the terms, similarity, identity, andhomology each have a distinct meaning as appreciated in the field ofgenetics. Moreover, orthology and paralogy can be important conceptsdescribing the relationship of members of a given protein family in oneorganism to the members of the same family in other organisms.

[0177] Amino acid abbreviations are provided in Table II. Conservativeamino acid substitutions can frequently be made in a protein withoutaltering either the conformation or the function of the protein.Proteins of the invention can comprise 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15 conservative substitutions. Such changes includesubstituting any of isoleucine (I), valine (V), and leucine (L) for anyother of these hydrophobic amino acids; aspartic acid (D) for glutamicacid (E) and vice versa; glutamine (Q) for asparagine (N) and viceversa; and serine (S) for threonine (T) and vice versa. Othersubstitutions can also be considered conservative, depending on theenvironment of the particular amino acid and its role in thethree-dimensional structure of the protein. For example, glycine (G) andalanine (A) can frequently be interchangeable, as can alanine (A) andvaline (V). Methionine (M), which is relatively hydrophobic, canfrequently be interchanged with leucine and isoleucine, and sometimeswith valine. Lysine (K) and arginine (R) are frequently interchangeablein locations in which the significant feature of the amino acid residueis its charge and the differing pK's of these two amino acid residuesare not significant. Still other changes can be considered“conservative” in particular environments (see, e.g. Table III herein;pages 13-15 “Biochemistry” 2^(nd) ED. Lubert Stryer ed (StanfordUniversity); Henikoff et al., PNAS 1992 Vol 89 10915-10919; Lei et al.,J Biol Chem May 19, 1995; 270(20):11882-6).

[0178] Embodiments of the invention disclosed herein include a widevariety of art-accepted variants or analogs of 151P3D4 proteins such aspolypeptides having amino acid insertions, deletions and substitutions.151P3D4 variants can be made using methods known in the art such assite-directed mutagenesis, alanine scanning, and PCR mutagenesis.Site-directed mutagenesis (Carter et al., Nucl. Acids Res., 13:4331(1986); Zoller et al., Nucl. Acids Res., 10:6487 (1987)), cassettemutagenesis (Wells et al., Gene, 34:315 (1985)), restriction selectionmutagenesis (Wells et al., Philos. Trans. R. Soc. London SerA, 317:415(1986)) or other known techniques can be performed on the cloned DNA toproduce the 151P3D4 variant DNA.

[0179] Scanning amino acid analysis can also be employed to identify oneor more amino acids along a contiguous sequence that is involved in aspecific biological activity such as a protein-protein interaction.Among the preferred scanning amino acids are relatively small, neutralamino acids. Such amino acids include alanine, glycine, serine, andcysteine. Alanine is typically a preferred scanning amino acid amongthis group because it eliminates the side-chain beyond the beta-carbonand is less likely to alter the main-chain conformation of the variant.Alanine is also typically preferred because it is the most common aminoacid. Further, it is frequently found in both buried and exposedpositions (Creighton, The Proteins, (W. H. Freeman & Co., N.Y.);Chothia, J. Mol. Biol., 150:1 (1976)). If alanine substitution does notyield adequate amounts of variant, an isosteric amino acid can be used.

[0180] As defined herein, 151P3D4 variants, analogs or homologs, havethe distinguishing attribute of having at least one epitope that is“cross reactive” with a 151P3D4 protein having an amino acid sequence ofFIG. 3. As used in this sentence, “cross reactive” means that anantibody or T cell that specifically binds to a 151P3D4 variant alsospecifically binds to a 151P3D4 protein having an amino acid sequenceset forth in FIG. 3. A polypeptide ceases to be a variant of a proteinshown in FIG. 3, when it no longer contains any epitope capable of beingrecognized by an antibody or T cell that specifically binds to thestarting 151P3D4 protein. Those skilled in the art understand thatantibodies that recognize proteins bind to epitopes of varying size, anda grouping of the order of about four or five amino acids, contiguous ornot, is regarded as a typical number of amino acids in a minimalepitope. See, e.g., Nair et al., J. Immunol 2000 165(12): 6949-6955;Hebbes et al., Mol Immunol (1989) 26(9):865-73; Schwartz et al., JImmunol (1985) 135(4):259

[0181] Other classes of 151P3D4-related protein variants share 70%, 75%,80%, 85% or 90% or more similarity with an amino acid sequence of FIG.3, or a fragment thereof. Another specific class of 151P3D4 proteinvariants or analogs comprise one or more of the 151P3D4 biologicalmotifs described herein or presently known in the art. Thus, encompassedby the present invention are analogs of 151P3D4 fragments (nucleic oramino acid) that have altered functional (e.g. immunogenic) propertiesrelative to the starting fragment. It is to be appreciated that motifsnow or which become part of the art are to be applied to the nucleic oramino acid sequences of FIG. 2 or FIG. 3.

[0182] As discussed herein, embodiments of the claimed invention includepolypeptides containing less than the full amino acid sequence of a151P3D4 protein shown in FIG. 2 or FIG. 3. For example, representativeembodiments of the invention comprise peptides/proteins having any 4, 5,6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more contiguous amino acids of a151P3D4 protein shown in FIG. 2 or FIG. 3.

[0183] Moreover, representative embodiments of the invention disclosedherein include polypeptides consisting of about amino acid 1 to abqutamino acid 10 of a 151P3D4 protein shown in FIG. 2 or FIG. 3,polypeptides consisting of about amino acid 10 to about amino acid 20 ofa 151P3D4 protein shown in FIG. 2 or FIG. 3, polypeptides consisting ofabout amino acid 20 to about amino acid 30 of a 151P3D4 protein shown inFIG. 2 or FIG. 3, polypeptides consisting of about amino acid 30 toabout amino acid 40 of a 151P3D4 protein shown in FIG. 2 or FIG. 3,polypeptides consisting of about amino acid 40 to about amino acid 50 ofa 151P3D4 protein shown in FIG. 2 or FIG. 3, polypeptides consisting ofabout amino acid 50 to about amino acid 60 of a 151P3D4 protein shown inFIG. 2 or FIG. 3, polypeptides consisting of about amino acid 60 toabout amino acid 70 of a 151P3D4 protein shown in FIG. 2 or FIG. 3,polypeptides consisting of about amino acid 70 to about amino acid 80 ofa 151P3D4 protein shown in FIG. 2 or FIG. 3, polypeptides consisting ofabout amino acid 80 to about amino acid 90 of a 151P3D4 protein shown inFIG. 2 or FIG. 3, polypeptides consisting of about amino acid 90 toabout amino acid 100 of a 151P3D4 protein shown in FIG. 2 or FIG. 3,etc. throughout the entirety of a 151P3D4 amino acid sequence. Moreover,polypeptides consisting of about amino acid 1 (or 20 or 30 or 40 etc.)to about amino acid 20, (or 130, or 140 or 150 etc.) of a 151P3D4protein shown in FIG. 2 or FIG. 3 are embodiments the invention. It isto be appreciated that the starting and stopping positions in thisparagraph refer to the specified position as well as that position plusor minus 5 residues.

[0184] 151P3D4-related proteins are generated using standard peptidesynthesis technology or using chemical cleavage methods well known inthe art. Alternatively, recombinant methods can be used to generatenucleic acid molecules that encode a 151P3D4-related protein. In oneembodiment, nucleic acid molecules provide a means to generate definedfragments of a 151P3D4 protein (or variants, homologs or analogsthereof).

[0185] III.A.) Motif-Bearing Protein Embodiments

[0186] Additional illustrative embodiments of the invention disclosedherein include 151P3D4 polypeptides comprising the amino acid residuesof one or more of the biological motifs contained within a 151P3D4polypeptide sequence set forth in FIG. 2 or FIG. 3. Various motifs areknown in the art, and a protein can be evaluated for the presence ofsuch motifs by a number of publicly available Internet sites (see, e.g.,URL addresses: pfam.wustl.edu/;http://searchlauncher.bcm.tmc.edu/seq-search/struc-predict.html;psort.ims.u-tokyo.ac.jp/; www.cbs.dtu.dk/;www.ebi.ac.uk/interpro/scan.html; www.expasy.ch/tools/scnpsit1.html;Epimatrix™ and Epimer™, Brown University,www.brown.edu/Research/TB-HIV_Lab/epimatrix/epimatrix.html; and BIMAS,bimas.dcrt.nih.gov/.).

[0187] Motif bearing subsequences of all 151P3D4 variant proteins areset forth and identified in Tables V-XVIII and XXII-LII.

[0188] Table XIX sets forth several frequently occurring motifs based onpfam searches (see URL address pfam.wustl.edu/). The columns of TableXIX list (1) motif name abbreviation, (2) percent identity found amongstthe different member of the motif family, (3) motif name or descriptionand (4) most common function; location information is included if themotif is relevant for location.

[0189] Polypeptides comprising one or more of the 151P3D4 motifsdiscussed above are useful in elucidating the specific characteristicsof a malignant phenotype in view of the observation that the 151P3D4motifs discussed above are associated with growth dysregulation andbecause 151P3D4 is overexpressed in certain cancers (See, e.g., TableI). Casein kinase II, cAMP and camp-dependent protein kinase, andProtein Kinase C, for example, are enzymes known to be associated withthe development of the malignant phenotype (see e.g. Chen et al., LabInvest., 78(2): 165-174 (1998); Gaiddon et al., Endocrinology 136(10):4331-4338 (1995); Hall et al., Nucleic Acids Research 24(6): 1119-1126(1996); Peterziel et al. Oncogene 18(46): 6322-6329 (1999) and O'Brian,Oncol. Rep. 5(2): 305-309 (1998)). Moreover, both glycosylation andmyristoylation are protein modifications also associated with cancer andcancer progression (see e.g. Dennis et al., Biochem. Biophys. Acta1473(1):21-34 (1999); Raju et al., Exp. Cell Res. 235(1): 145-154(1997)). Amidation is another protein modification also associated withcancer and cancer progression (see e.g. Treston et al., J. Natl. CancerInst. Monogr. (13): 169-175 (1992)).

[0190] In another embodiment, proteins of the invention comprise one ormore of the immunoreactive epitopes identified in accordance withart-accepted methods, such as the peptides set forth in Tables V-XVIIIand XXII-LI. CTL epitopes can be determined using specific algorithms toidentify peptides within a 151P3D4 protein that are capable of optimallybinding to specified HLA alleles (e.g., Table IV; Epimatrix™ andEpimer™, Brown University, URLwww.brown.edu/Research/TB-HIV_Lab/epimatrix/epimatrix.html; and BIMAS,URL bimas.dcrt.nih.gov/.) Moreover, processes for identifying peptidesthat have sufficient binding affinity for HLA molecules and which arecorrelated with being immunogenic epitopes, are well known in the art,and are carried out without undue experimentation. In addition,processes for identifying peptides that are immunogenic epitopes, arewell known in the art, and are carried out without undue experimentationeither in vitro or in vivo.

[0191] Also known in the art are principles for creating analogs of suchepitopes in order to modulate immunogenicity. For example, one beginswith an epitope that bears a CTL or HTL motif (see, e.g., the HLA ClassI and HLA Class II motifs/supermotifs of Table IV). The epitope isanaloged by substituting out an amino acid at one of the specifiedpositions, and replacing it with another amino acid specified for thatposition. For example, one can substitute out a deleterious residue infavor of any other residue, such as a preferred residue as defined inTable IV; substitute a less-preferred residue with a preferred residueas defined in Table IV; or substitute an originally-occurring preferredresidue with another preferred residue as defined in Table IV.Substitutions can occur at primary anchor positions or at otherpositions in a peptide; see, e.g., Table IV.

[0192] A variety of references reflect the art regarding theidentification and generation of epitopes in a protein of interest aswell as analogs thereof. See, for example, WO 97/33602 to Chesnut etal.; Sette, Immunogenetics 1999 50(34): 201-212; Sette et al., J.Immunol. 2001 166(2): 1389-1397; Sidney et al., Hum. Immunol. 199758(1): 12-20; Kondo et al., Immunogenetics 1997 45(4): 249-258; Sidneyet al., J. Immunol. 1996 157(8): 3480-90; and Falk et al., Nature 351:290-6 (1991); Hunt et al., Science 255:1261-3 (1992); Parker et al., J.Immunol. 149:3580-7 (1992); Parker et al., J. Immunol. 152:163-75(1994)) Kast et al., 1994 152(8): 3904-12; Borras-Cuesta et al., Hum.Immunol. 2000 61(3): 266-278; Alexander et al., J. Immnunol. 2000164(3); 164(3): 1625-1633; Alexander et al., PMID: 7895164, UI:95202582; O'Sullivan et al., J. Immunol. 1991 147(8): 2663-2669;Alexander et al, Immunity 1994 1(9): 751-761 and Alexander et al.,Immunol. Res. 1998 18(2): 79-92.

[0193] Related embodiments of the invention include polypeptidescomprising combinations of the different motifs set forth in Table XX,and/or, one or more of the predicted CTL epitopes of Tables V-XVII andXXII-XLVII, and/or, one or more of the predicted HTL epitopes of TablesXLVIII-LI, and/or, one or more of the T cell binding motifs known in theart. Preferred embodiments contain no insertions, deletions orsubstitutions either within the motifs or the intervening sequences ofthe polypeptides. In addition, embodiments which include a number ofeither N-terminal and/or C-terminal amino acid residues on either sideof these motifs may be desirable (to, for example, include a greaterportion of the polypeptide architecture in which the motif is located).Typically the number of N-terminal and/or C-terminal amino acid residueson either side of a motif is between about 1 to about 100 amino acidresidues, preferably 5 to about 50 amino acid residues.

[0194] 151P3D4-related proteins are embodied in many forms, preferablyin isolated form. A purified 151P3D4 protein molecule will besubstantially free of other proteins or molecules that impair thebinding of 151P3D4 to antibody, T cell or other ligand. The nature anddegree of isolation and purification will depend on the intended use.Embodiments of a 151P3D4-related proteins include purified151P3D4-related proteins and functional, soluble 151P3D4-relatedproteins. In one embodiment, a functional, soluble 151P3D4 protein orfragment thereof retains the ability to be bound by antibody, T cell orother ligand.

[0195] The invention also provides 151P3D4 proteins comprisingbiologically active fragments of a 151P3D4 amino acid sequence shown inFIG. 2 or FIG. 3. Such proteins exhibit properties of the starting151P3D4 protein, such as the ability to elicit the generation ofantibodies that specifically bind an epitope associated with thestarting 151P3D4 protein; to be bound by such antibodies; to elicit theactivation of HTL or CTL; and/or, to be recognized by HTL or CTL thatalso specifically bind to the starting protein. 15P3D4-relatedpolypeptides that contain particularly interesting structures can bepredicted and/or identified using various analytical techniques wellknown in the art, including, for example, the methods of Chou-Fasman,Garnier-Robson, Kyte-Doolittle, Eisenberg, Karplus-Schultz orJameson-Wolf analysis, or on the basis of immunogenicity. Fragments thatcontain such structures are particularly useful in generatingsubunit-specific anti-151P3D4 antibodies, or T cells or in identifyingcellular factors that bind to 151P3D4. For example, hydrophilicityprofiles can be generated, and immunogenic peptide fragments identified,using the method of Hopp, T. P. and Woods, K. R., 1981, Proc. Natl.Acad. Sci. U.S.A. 78:3824-3828. Hydropathicity profiles can begenerated, and immunogenic peptide fragments identified, using themethod of Kyte, J. and Doolittle, R. F., 1982, J. Mol. Biol.157:105-132. Percent (%) Accessible Residues profiles can be generated,and immunogenic peptide fragments identified, using the method of JaninJ., 1979, Nature 277:491-492. Average Flexibility profiles can begenerated, and immunogenic peptide fragments identified, using themethod of Bhaskaran R., Ponnuswamy P. K., 1988, Int. J. Pept. ProteinRes. 32:242-255. Beta-turn profiles can be generated, and immunogenicpeptide fragments identified, using the method of Deleage, G., Roux B.,1987, Protein Engineering 1:289-294.

[0196] CTL epitopes can be determined using specific algorithms toidentify peptides within a 151P3D4 protein that are capable of optimallybinding to specified HLA alleles (e.g., by using the SYFPEITHI site atWorld Wide Web URL syfpeithi.bmi-heidelberg.com/; the listings in TableIV(A)-(E); Epimatrix™ and Epimer™, Brown University, URL(www.brown.edu/Research/TB-HIV_Lab/epimatrix/epimatrix.html); and BIMAS,URL bimas.dcrt.nih.gov/). Illustrating this, peptide epitopes from151P3D4 that are presented in the context of human MHC Class Imolecules, e.g., HLA-A1, A2, A3, A11, A24, B7 and B35 were predicted(see, e.g., Tables V-XVIII, XXII-LI). Specifically, the complete aminoacid sequence of the 151P3D4 protein and relevant portions of othervariants, i.e., for HLA Class I predictions 9 flanking residues oneither side of a point mutation, and for HLA Class II predictions 14flanking residues on either side of a point mutation, were entered intothe HLA Peptide Motif Search algorithm found in the Bioinformatics andMolecular Analysis Section (BIMAS) web site listed above; in addition tothe site SYFPEITHI, at URL syfpeithi.bmi-heidelberg.com/.

[0197] The HLA peptide motif search algorithm was developed by Dr. KenParker based on binding of specific peptide sequences in the groove ofHLA Class I molecules, in particular HLA-A2 (see, e.g., Falk et al.,Nature 351: 290-6 (1991); Hunt et al., Science 255:1261-3 (1992); Parkeret al., J. Immunol. 149:3580-7 (1992); Parker et al., J. Immunol.152:163-75 (1994)). This algorithm allows location and ranking of 8-mer,9-mer, and 10-mer peptides from a complete protein sequence forpredicted binding to HLA-A2 as well as numerous other HLA Class Imolecules. Many HLA class I binding peptides are 8-, 9-, 10 or 11-mers.For example, for Class I HLA-A2, the epitopes preferably contain aleucine (L) or methionine (M) at position 2 and a valine (V) or leucine(L) at the C-terminus (see, e.g., Parker et al., J. Immunol. 149:3580-7(1992)). Selected results of 151P3D4 predicted binding peptides areshown in Tables V-XVIII and XXII-LI herein. In Tables V-XVIII andXXII-XLVII, selected candidates, 9-mers and 10-mers, for each familymember are shown along with their location, the amino acid sequence ofeach specific peptide, and an estimated binding score. In TablesXLVIII-LI, selected candidates, 15-mers, for each family member areshown along with their location, the amino acid sequence of eachspecific peptide, and an estimated binding score. The binding scorecorresponds to the estimated half time of dissociation of complexescontaining the peptide at 37° C. at pH 6.5. Peptides with the highestbinding score are predicted to be the most tightly bound to HLA Class Ion the cell surface for the greatest period of time and thus representthe best immunogenic targets for T-cell recognition.

[0198] Actual binding of peptides to an HLA allele can be evaluated bystabilization of HLA expression on the antigen-processing defective cellline T2 (see, e.g., Xue et al., Prostate 30:73-8 (1997) and Peshwa etal., Prostate 36:129-38 (1998)). Immunogenicity of specific peptides canbe evaluated in vitro by stimulation of CD8+ cytotoxic T lymphocytes(CTL) in the presence of antigen presenting cells such as dendriticcells.

[0199] It is to be appreciated that every epitope predicted by the BIMASsite, Epimer™ and Epimatrix™ sites, or specified by the HLA class I orclass II motifs available in the art or which become part of the artsuch as set forth in Table IV (or determined using World Wide Web siteURL syfpeithi.bmi-heidelberg.com/, or BIMAS, bimas.dcrt.nih.gov/) are tobe “applied” to a 151P3D4 protein in accordance with the invention. Asused in this context “applied” means that a 151P3D4 protein isevaluated, e.g., visually or by computer-based patterns finding methods,as appreciated by those of skill in the relevant art. Every subsequenceof a 151P3D4 protein of 8, 9, 10, or 11 amino acid residues that bearsan HLA Class I motif, or a subsequence of 9 or more amino acid residuesthat bear an HLA Class II motif are within the scope of the invention.

[0200] III.B.) Expression of 151P3D4-Related Proteins

[0201] In an embodiment described in the examples that follow, 151P3D4can be conveniently expressed in cells (such as 293T cells) transfectedwith a conmmercially available expression vector such as a CMV-drivenexpression vector encoding 151P3D4 with a C-terminal 6XHis and MYC tag(pcDNA3.1/mycHIS, Invitrogen or TagS, GenHunter Corporation, NashvilleTenn.). The TagS vector provides an IgGK secretion signal that can beused to facilitate the production of a secreted 151P3D4 protein intransfected cells. The secreted HIS-tagged 151P3D4 in the culture mediacan be purified, e.g., using a nickel column using standard techniques.

[0202] III.C.) Modifications of 151P3D4-Related Proteins

[0203] Modifications of 151P3D4-related proteins such as covalentmodifications are included within the scope of this invention. One typeof covalent modification includes reacting targeted amino acid residuesof a 151P3D4 polypeptide with an organic derivatizing agent that iscapable of reacting with selected side chains or the N- or C-terminalresidues of a 151P3D4 protein. Another type of covalent modification ofa 151P3D4 polypeptide included within the scope of this inventioncomprises altering the native glycosylation pattern of a protein of theinvention. Another type of covalent modification of 151P3D4 compriseslinking a 151P3D4 polypeptide to one of a variety of nonproteinaceouspolymers, e.g., polyethylene glycol (PEG), polypropylene glycol, orpolyoxyalkylenes, in the manner set forth in U.S. Pat. Nos. 4,640,835;4,496,689; 4,301,144; 4,670,417; 4,791,192 or 4,179,337.

[0204] The 151P3D4-related proteins of the present invention can also bemodified to form a chimeric molecule comprising 151P3D4 fused toanother, heterologous polypeptide or amino acid sequence. Such achimeric molecule can be synthesized chemically or recombinantly. Achimeric molecule can have a protein of the invention fused to anothertumor-associated antigen or fragment thereof. Alternatively, a proteinin accordance with the invention can comprise a fusion of fragments of a151P3D4 sequence (amino or nucleic acid) such that a molecule is createdthat is not, through its length, directly homologous to the amino ornucleic acid sequences shown in FIG. 2 or FIG. 3. Such a chimericmolecule can comprise multiples of the same subsequence of 151P3D4. Achimeric molecule can comprise a fusion of a 151P3D4-related proteinwith a polyhistidine epitope tag, which provides an epitope to whichimmobilized nickel can selectively bind, with cytokines or with growthfactors. The epitope tag is generally placed at the amino- orcarboxyl-terminus of a 151P3D4 protein. In an alternative embodiment,the chimeric molecule can comprise a fusion of a 151P3D4-related proteinwith an immunoglobulin or a particular region of an immunoglobulin. Fora bivalent form of the chimeric molecule (also referred to as an“immunoadhesin”), such a fusion could be to the Fc region of an IgGmolecule. The Ig fusions preferably include the substitution of asoluble (transmembrane domain deleted or inactivated) form of a 151P3D4polypeptide in place of at least one variable region within an Igmolecule. In a preferred embodiment, the immunoglobulin fusion includesthe hinge, CH2 and CH3, or the hinge, CHI, CH2 and CH3 regions of anIgGI molecule. For the production of immunoglobulin fusions see, e.g.,U.S. Pat. No. 5,428,130 issued Jun. b 27, 1995.

[0205] III.D.) Uses of 151P3D4-Related Proteins

[0206] The proteins of the invention have a number of different specificuses. As 151P3D4 is highly expressed in prostate and other cancers,151P3D4-related proteins are used in methods that assess the status of151P3D4 gene products in normal versus cancerous tissues, therebyelucidating the malignant phenotype. Typically, polypeptides fromspecific regions of a 151P3D4 protein are used to assess the presence ofperturbations (such as deletions, insertions, point mutations etc.) inthose regions (such as regions containing one or more motifs). Exemplaryassays utilize antibodies or T cells targeting 151P3D4-related proteinscomprising the amino acid residues of one or more of the biologicalmotifs contained within a 151P3D4 polypeptide sequence in order toevaluate the characteristics of this region in normal versus canceroustissues or to elicit an immune response to the epitope. Alternatively,151P3D4-related proteins that contain the amino acid residues of one ormore of the biological motifs in a 151P3D4 protein are used to screenfor factors that interact with that region of 151P3D4.

[0207] 151P3D4 protein fragments/subsequences are particularly useful ingenerating and characterizing domain-specific antibodies (e.g.,antibodies recognizing an extracellular or intracellular epitope of a151P3D4 protein), for identifying agents or cellular factors that bindto 151P3D4 or a particular structural domain thereof, and in varioustherapeutic and diagnostic contexts, including but not limited todiagnostic assays, cancer vaccines and methods of preparing suchvaccines.

[0208] Proteins encoded by the 151P3D4 genes, or by analogs, homologs orfragments thereof, have a variety of uses, including but not limited togenerating antibodies and in methods for identifying ligands and otheragents and cellular constituents that bind to a 151P3D4 gene product.Antibodies raised against a 151P3D4 protein or fragment thereof areuseful in diagnostic and prognostic assays, and imaging methodologies inthe management of human cancers characterized by expression of 151P3D4protein, such as those listed in Table I. Such antibodies can beexpressed intracellularly and used in methods of treating patients withsuch cancers. 151P3D4-related nucleic acids or proteins are also used ingenerating HTL or CTL responses.

[0209] Various immunological assays useful for the detection of 151P3D4proteins are used, including but not limited to various types ofradioimmunoassays, enzyme-linked immunosorbent assays (ELISA),enzyme-linked immunofluorescent assays (ELIFA), immunocytochemicalmethods, and the like. Antibodies can be labeled and used asimmunological imaging reagents capable of detecting 151P3D4-expressingcells (e.g., in radioscintigraphic imaging methods). 151P3D4 proteinsare also particularly useful in generating cancer vaccines, as furtherdescribed herein.

[0210] IV.) 151P3D4 Antibodies

[0211] Another aspect of the invention provides antibodies that bind to151P3D4-related proteins. Preferred antibodies specifically bind to a151P3D4-related protein and do not bind (or bind weakly) to peptides orproteins that are not 151P3D4-related proteins. For example, antibodiesthat bind 151P3D4 can bind 151P3D4-related proteins such as the homologsor analogs thereof.

[0212] 151P3D4 antibodies of the invention are particularly useful incancer (see, e.g., Table I) diagnostic and prognostic assays, andimaging methodologies. Similarly, such antibodies are useful in thetreatment, diagnosis, and/or prognosis of other cancers, to the extent151P3D4 is also expressed or overexpressed in these other cancers.Moreover, intracellularly expressed antibodies (e.g., single chainantibodies) are therapeutically useful in treating cancers in which theexpression of 151P3D4 is involved, such as advanced or metastaticprostate cancers.

[0213] The invention also provides various immunological assays usefulfor the detection and quantification of 151P3D4 and mutant151P3D4-related proteins. Such assays can comprise one or more 151P3D4antibodies capable of recognizing and binding a 151P3D4-related protein,as appropriate. These assays are performed within various immunologicalassay formats well known in the art, including but not limited tovarious types of radioimmunoassay, enzyme-linked immunosorbent assays(ELISA), enzyme-linked immunofluorescent assays (ELIFA), and the like.

[0214] Immunological non-antibody assays of the invention also compriseT cell immunogenicity assays (inhibitory or stimulatory) as well asmajor histocompatibility complex (MHC) binding assays.

[0215] In addition, immunological imaging methods capable of detectingprostate cancer and other cancers expressing 151P3D4 are also providedby the invention, including but not limited to radioscintigraphicimaging methods using labeled 151P3D4 antibodies. Such assays areclinically useful in the detection, monitoring, and prognosis of 151P3D4expressing cancers such as prostate cancer. 151P3D4 antibodies are alsoused in methods for purifying a 151P3D4-related protein and forisolating 151P3D4 homologues and related molecules. For example, amethod of purifying a 151P3D4-related protein comprises incubating a151P3D4 antibody, which has been coupled to a solid matrix, with alysate or other solution containing a 151P3D4-related protein underconditions that permit the 151P3D4 antibody to bind to 151P3D4-relatedprotein; washing the solid matrix to eliminate impurities; and elutingthe 151P3D4-related protein from the coupled antibody. Other uses of151P3D4 antibodies in accordance with the invention include generatinganti-idiotypic antibodies that mimic a 151P3D4 protein.

[0216] Various methods for the preparation of antibodies are well knownin the art. For example, antibodies can be prepared by immunizing asuitable mammalian host using a 151P3D4-related protein, peptide, orfragment, in isolated or immunoconjugated form (Antibodies: A LaboratoryManual, CSH Press, Eds., Harlow, and Lane (1988); Harlow, Antibodies,Cold Spring Harbor Press, NY (1989)). In addition, fusion proteins of151P3D4 can also be used, such as a 151P3D4 GST-fusion protein. In aparticular embodiment, a GST fusion protein comprising all or most ofthe amino acid sequence of FIG. 2 or FIG. 3 is produced, then used as animmunogen to generate appropriate antibodies. In another embodiment, a151P3D4-related protein is synthesized and used as an immunogen.

[0217] In addition, naked DNA immunization techniques known in the artare used (with or without purified 151P3D4-related protein or 151P3D4expressing cells) to generate an immune response to the encodedimmunogen (for review, see Donnelly et al., 1997, Ann. Rev. Immunol. 15:617-648).

[0218] The amino acid sequence of a 151P3D4 protein as shown in FIG. 2or FIG. 3 can be analyzed to select specific regions of the 151P3D4protein for generating antibodies. For example, hydrophobicity andhydrophilicity analyses of a 151P3D4 amino acid sequence are used toidentify hydrophilic regions in the 151P3D4 structure. Regions of a151P3D4 protein that show immunogenic structure, as well as other regiondomains, can readily be identified using various other methods known inthe art, such as Chou-Fasman, Garnier-Robson, Kyte-Doolittle, Eisenberg,Karplus-Schultz or Jameson-Wolf analysis. Hydrophilicity profiles can begenerated using the method of Hopp, T. P. and Woods, K. R., 1981, Proc.Natl. Acad. Sci. U.S.A. 78:3824-3828. Hydropathicity profiles can begenerated using the method of Kyte, J. and Doolittle, R. F., 1982, J.Mol. Biol. 157:105-132. Percent (%) Accessible Residues profiles can begenerated using the method of Janin J., 1979, Nature 277:491-492.Average Flexibility profiles can be generated using the method ofBhaskaran R., Ponnuswamy P. K., 1988, Int. J. Pept. Protein Res.32:242-255. Beta-turn profiles can be generated using the method ofDeleage, G., Roux B., 1987, Protein Engineering 1:289-294. Thus, eachregion identified by any of these programs or methods is within thescope of the present invention. Methods for the generation of 151P3D4antibodies are further illustrated by way of the examples providedherein. Methods for preparing a protein or polypeptide for use as animmunogen are well known in the art. Also well known in the art aremethods for preparing immunogenic conjugates of a protein with acarrier, such as BSA, KLH or other carrier protein. In somecircumstances, direct conjugation using, for example, carbodiimidereagents are used; in other instances linking reagents such as thosesupplied by Pierce Chemical Co., Rockford, Ill., are effective.Administration of a 151P3D4 immunogen is often conducted by injectionover a suitable time period and with use of a suitable adjuvant, as isunderstood in the art. During the immunization schedule, titers ofantibodies can be taken to determine adequacy of antibody formation.

[0219] 151P3D4 monoclonal antibodies can be produced by various meanswell known in the art. For example, immortalized cell lines that secretea desired monoclonal antibody are prepared using the standard hybridomatechnology of Kohler and Milstein or modifications that immortalizeantibody-producing B cells, as is generally known. Immortalized celllines that secrete the desired antibodies are screened by immunoassay inwhich the antigen is a 151P3D4-related protein. When the appropriateimmortalized cell culture is identified, the cells can be expanded andantibodies produced either from in vitro cultures or from ascites fluid.

[0220] The antibodies or fragments of the invention can also beproduced, by recombinant means. Regions that bind specifically to thedesired regions of a 151P3D4 protein can also be produced in the contextof chimeric or complementarity determining region (CDR) graftedantibodies of multiple species origin. Humanized or human 151P3D4antibodies can also be produced, and are preferred for use intherapeutic contexts. Methods for humanizing murine and other non-humanantibodies, by substituting one or more of the non-human antibody CDRsfor corresponding human antibody sequences, are well known (see forexample, Jones et al., 1986, Nature 321: 522-525; Riechann et al., 1988,Nature332: 323-327; Verhoeyen et al., 1988, Science 239: 1534-1536). Seealso, Carter et al., 1993, Proc. Natl. Acad. Sci. USA 89: 4285 and Simset al., 1993, J. Immunol. 151: 2296.

[0221] Methods for producing fully human monoclonal antibodies includephage display and transgenic methods (for review, see Vaughan et a.,1998, Nature Biotechnology 16: 535-539). Fully human 151P3D4 monoclonalantibodies can be generated using cloning technologies employing largehuman Ig gene combinatorial libraries (i.e., phage display) (Griffithsand Hoogenboom, Building an in vitro immune system: human antibodiesfrom phage display libraries. In: Protein Engineering of AntibodyMolecules for Prophylactic and Therapeutic Applications in Man, Clark,M. (Ed.), Nottingham Academic, pp 45-64 (1993); Burton and Barbas, HumanAntibodies from combinatorial libraries. Id., pp 65-82). Fully human151P3D4 monoclonal antibodies can also be produced using transgenic miceengineered to contain human immunoglobulin gene loci as described in PCTPatent Application WO98/24893, Kucherlapati and Jakobovits et al.,published Dec. 3, 1997 (see also, Jakobovits, 1998, Exp. Opin. Invest.Drugs 7(4): 607-614; U.S. Pat. Nos. 6,162,963 issued Dec. 19, 2000;6,150,584 issued Nov. 12, 2000; and, 6,114598 issued Sep. 5, 2000). Thismethod avoids the in vitro manipulation required with phage displaytechnology and efficiently produces high affinity authentic humanantibodies.

[0222] Reactivity of 151P3D4 antibodies with a 151P3D4-related proteincan be established by a number of well known means, including Westernblot, immunoprecipitation, ELISA, and FACS analyses using, asappropriate, 151P3D4-related proteins, 151P3D4-expressing cells orextracts thereof. A 151P3D4 antibody or fragment thereof can be labeledwith a detectable marker or conjugated to a second molecule. Suitabledetectable markers include, but are not limited to, a radioisotope, afluorescent compound, a bioluminescent compound, chemiluminescentcompound, a metal chelator or an enzyme. Further, bi-specific antibodiesspecific for two or more 151P3D4 epitopes are generated using methodsgenerally known in the art. Homodimeric antibodies can also be generatedby cross-linking techniques known in the art (e.g., Wolff et al., CancerRes. 53: 2560-2565).

[0223] V.) 151P3D4 Cellular Immune Responses

[0224] The mechanism by which T cells recognize antigens has beendelineated. Efficacious peptide epitope vaccine compositions of theinvention induce a therapeutic or prophylactic immune responses in verybroad segments of the world-wide population. For an understanding of thevalue and efficacy of compositions of the invention that induce cellularimmune responses, a brief review of immunology-related technology isprovided.

[0225] A complex of an HLA molecule and a peptidic antigen acts as theligand recognized by HLA-restricted T cells (Buus, S. et al., Cell47:1071, 1986; Babbitt, B. P. et al., Nature 317:359, 1985; Townsend, A.and Bodmer, H., Annu. Rev. Immunol. 7:601, 1989; Germain, R. N., Annu.Rev. Immunol. 11:403, 1993). Through the study of single amino acidsubstituted antigen analogs and the sequencing of endogenously bound,naturally processed peptides, critical residues that correspond tomotifs required for specific binding to HLA antigen molecules have beenidentified and are set forth in Table IV (see also, e.g., Southwood, etal., J. Immunol. 160:3363, 1998; Rammensee, et al., Immunogenetics41:178, 1995; Rammensee et al., SYFPEITHI, access via World Wide Web atURL syfpeithi.bmi-heidelberg.com/; Sette, A. and Sidney, J. Curr. Opin.Immunol. 10:478, 1998; Engelhard, V. H.,Curr. Opin. Immunol. 6:13, 1994;Sette, A. and Grey, H. M., Curr. Opin. Immunol. 4:79, 1992; Sinigaglia,F. and Hammer, J. Curr. Biol. 6:52, 1994; Ruppert et al., Cell74:929-937, 1993; Kondo et al., J. Immunol. 155:4307-4312, 1995; Sidneyet al., J. Immunol. 157:3480-3490, 1996; Sidney et al., Human Immunol.45:79-93, 1996; Sette, A. and Sidney, J. Immunogenetics November 1999;50(3-4):201-12, Review).

[0226] Furthermore, x-ray crystallographic analyses of HLA-peptidecomplexes have revealed pockets within the peptide binding cleft/grooveof HLA molecules which accommodate, in an allele-specific mode, residuesborne by peptide ligands; these residues in turn determine the HLAbinding capacity of the peptides in which they are present. (See, e.g.,Madden, D. R. Annu. Rev. Immunol. 13:587, 1995; Smith, et al., Immunity4:203, 1996; Fremont et al., Immunity 8:305, 1998; Stern et al.,Structure 2:245, 1994; Jones, E. Y. Curr. Opin. Immunol. 9:75, 1997;Brown, J. H. et al., Nature 364:33, 1993; Guo, H. C. et al., Proc. Natl.Acad. Sci. USA 90:8053, 1993; Guo, H. C. et al., Nature 360:364, 1992;Silver, M. L. et al., Nature 360:367, 1992; Matsumura, M. et al.,Science 257:927, 1992; Madden et al., Cell 70:1035, 1992; Fremont, D. H.et al., Science 257:919, 1992; Saper, M. A., Bjorkman, P. J. and Wiley,D. C., J. Mol. Biol. 219:277, 1991.)

[0227] Accordingly, the definition of class I and class IIallele-specific HLA binding motifs, or class I or class II supermotifsallows identification of regions within a protein that are correlatedwith binding to particular HLA antigen(s).

[0228] Thus, by a process of HLA motif identification, candidates forepitope-based vaccines have been identified; such candidates can befurther evaluated by HLA-peptide binding assays to determine bindingaffinity and/or the time period of association of the epitope and itscorresponding HLA molecule. Additional confirmatory work can beperformed to select, amongst these vaccine candidates, epitopes withpreferred characteristics in terms of population coverage, and/orimmunogenicity.

[0229] Various strategies can be utilized to evaluate cellularimmunogenicity, including:

[0230] 1) Evaluation of primary T cell cultures from normal individuals(see, e.g., Wentworth, P. A. et al., Mol. Immunol. 32:603, 1995; Celis,E. et al., Proc. Natl. Acad. Sci. USA 91:2105, 1994; Tsai, V. et al., J.Immunol. 158:1796, 1997; Kawashima, I. et al., Human Immunol. 59:1,1998). This procedure involves the stimulation of peripheral bloodlymphocytes (PBL) from normal subjects with a test peptide in thepresence of antigen presenting cells in vitro over a period of severalweeks. T cells specific for the peptide become activated during thistime and are detected using, e.g., a lymphokine- or ⁵¹Cr-release assayinvolving peptide sensitized target cells.

[0231] 2) Immunization of HLA transgenic mice (see, e.g., Wentworth, P.A. et al., J. Immunol. 26:97, 1996; Wentworth, P. A. et al., Int.Immunol. 8:651, 1996; Alexander, J. et al., J. Immunol. 159:4753, 1997).For example, in such methods peptides in incomplete Freund's adjuvantare administered subcutaneously to HLA transgenic mice. Several weeksfollowing immunization, splenocytes are removed and cultured in vitro inthe presence of test peptide for approximately one week.Peptide-specific T cells are detected using, e.g., a ⁵¹Cr-release assayinvolving peptide sensitized target cells and target cells expressingendogenously generated antigen.

[0232] 3) Demonstration of recall T cell responses from immuneindividuals who have been either effectively vaccinated and/or fromchronically ill patients (see, e.g., Rehermann, B. et al., J. Exp. Med.181:1047, 1995; Doolan, D. L. et al., Immunity 7:97, 1997; Bertoni, R.et al., J. Clin. Invest. 100:503, 1997; Threlkeld, S. C. et al., J.Immunol. 159:1648, 1997; Diepolder, H. M. et al., J. Virol. 71:6011,1997). Accordingly, recall responses are detected by culturing PBL fromsubjects that have been exposed to the antigen due to disease and thushave generated an immune response “naturally”, or from patients who werevaccinated against the antigen. PBL from subjects are cultured in vitrofor 1-2 weeks in the presence of test peptide plus antigen presentingcells (APC) to allow activation of “memory” T cells, as compared to“naive” T cells. At the end of the culture period, T cell activity isdetected using assays including ⁵¹Cr release involvingpeptide-sensitized targets, T cell proliferation, or lymphokine release.

[0233] VI.) 151P3D4 Transzenic Animals

[0234] Nucleic acids that encode a 151P3D4-related protein can also beused to generate either transgenic animals or “knock out” animals that,in turn, are useful in the development and screening of therapeuticallyuseful reagents. In accordance with established techniques, cDNAencoding 151P3D4 can be used to clone genomic DNA that encodes 151P3D4.The cloned genomic sequences can then be used to generate transgenicanimals containing cells that express DNA that encode 151P3D4. Methodsfor generating transgenic animals, particularly animals such as mice orrats, have become conventional in the art and are described, forexample, in U.S. Pat. Nos. 4,736,866 issued Apr. 12, 1988, and 4,870,009issued Sep. 26, 1989. Typically, particular cells would be targeted for151P3D4 transgene incorporation with tissue-specific enhancers.

[0235] Transgenic animals that include a copy of a transgene encoding151P3D4 can be used to examine the effect of increased expression of DNAthat encodes 151P3D4. Such animals can be used as tester animals forreagents thought to confer protection from, for example, pathologicalconditions associated with its overexpression. In accordance with thisaspect of the invention, an animal is treated with a reagent and areduced incidence of a pathological condition, compared to untreatedanimals that bear the transgene, would indicate a potential therapeuticintervention for the pathological condition.

[0236] Alternatively, non-human homologues of 151P3D4 can be used toconstruct a 151P3D4 “knock out” animal that has a defective or alteredgene encoding 151P3D4 as a result of homologous recombination betweenthe endogenous gene encoding 151P3D4 and altered genomic DNA encoding151P3D4 introduced into an embryonic cell of the animal. For example,cDNA that encodes 151P3D4 can be used to clone genomic DNA encoding151P3D4 in accordance with established techniques. A portion of thegenomic DNA encoding 151P3D4 can be deleted or replaced with anothergene, such as a gene encoding a selectable marker that can be used tomonitor integration. Typically, several kilobases of unaltered flankingDNA (both at the 5′ and 3′ ends) are included in the vector (see, e.g.,Thomas and Capecchi, Cell 51:503 (1987) for a description of homologousrecombination vectors). The vector is introduced into an embryonic stemcell line (e.g., by electroporation) and cells in which the introducedDNA has homologously recombined with the endogenous DNA are selected(see, e.g., Li et al., Cell, 69:915 (1992)). The selected cells are theninjected into a blastocyst of an animal (e.g., a mouse or rat) to formaggregation chimeras (see, e.g., Bradley, in Teratocarcinomas andEmbryonic Stem Cells: A Practical Approach, E. J. Robertson, ed. (IRL,Oxford, 1987), pp. 113-152). A chimeric embryo can then be implantedinto a suitable pseudopregnant female foster animal, and the embryobrought to term to create a “knock out” animal. Progeny harboring thehomologously recombined DNA in their germ cells can be identified bystandard techniques and used to breed animals in which all cells of theanimal contain the homologously recombined DNA. Knock out animals can becharacterized, for example, for their ability to defend against certainpathological conditions or for their development of pathologicalconditions due to absence of a 151P3D4 polypeptide.

[0237] VII.) Methods for the Detection of 151P3D4

[0238] Another aspect of the present invention relates to methods fordetecting 151P3D4 polynucleotides and 151P3D4-related proteins, as wellas methods for identifying a cell that expresses 151P3D4. The expressionprofile of 151P3D4 makes it a diagnostic marker for metastasizeddisease. Accordingly, the status of 151P3D4 gene products providesinformation useful for predicting a variety of factors includingsusceptibility to advanced stage disease, rate of progression, and/ortumor aggressiveness. As discussed in detail herein, the status of151P3D4 gene products in patient samples can be analyzed by a varietyprotocols that are well known in the art including immunohistochemicalanalysis, the variety of Northern blotting techniques including in situhybridization, RT-PCR analysis (for example on laser capturemicro-dissected samples), Western blot analysis and tissue arrayanalysis.

[0239] More particularly, the invention provides assays for thedetection of 151P3D4 polynucleotides in a biological sample, such asserum, bone, prostate, and other tissues, urine, semen, cellpreparations, and the like. Detectable 151P3D4 polynucleotides include,for example, a 151P3D4 gene or fragment thereof, 151P3D4 mRNA,alternative splice variant 151P3D4 mRNAs, and recombinant DNA or RNAmolecules that contain a 151P3D4 polynucleotide. A number of methods foramplifying and/or detecting the presence of 151P3D4 polynucleotides arewell known in the art and can be employed in the practice of this aspectof the invention.

[0240] In one embodiment, a method for detecting a 151P3D4 mRNA in abiological sample comprises producing cDNA from the sample by reversetranscription using at least one primer; amplifying the cDNA so producedusing a 151P3D4 polynucleotides as sense and antisense primers toamplify 151P3D4 cDNAs therein; and detecting the presence of theamplified 151P3D4 cDNA. Optionally, the sequence of the amplified151P3D4 cDNA can be determined.

[0241] In another embodiment, a method of detecting a 151P3D4 gene in abiological sample comprises first isolating genomic DNA from the sample;amplifying the isolated genomic DNA using 151P3D4 polynucleotides assense and antisense primers; and detecting the presence of the amplified151P3D4 gene. Any number of appropriate sense and antisense probecombinations can be designed from a 151P3D4 nucleotide sequence (see,e.g., FIG. 2) and used for this purpose.

[0242] The invention also provides assays for detecting the presence ofa 151P3D4 protein in a tissue or other biological sample such as serum,semen, bone, prostate, urine, cell preparations, and the like. Methodsfor detecting a 151P3D4-related protein are also well known and include,for example, immunoprecipitation, immunohistochemical analysis, Westernblot analysis, molecular binding assays, ELISA, ELIFA and the like. Forexample, a method of detecting the presence of a 151P3D4-related proteinin a biological sample comprises first contacting the sample with a151P3D4 antibody, a 151P3D4-reactive fragment thereof, or a recombinantprotein containing an antigen binding region of a 151P3D4 antibody; andthen detecting the binding of 151P3D4-related protein in the sample.

[0243] Methods for identifying a cell that expresses 151P3D4 are alsowithin the scope of the invention. In one embodiment, an assay foridentifying a cell that expresses a 151P3D4 gene comprises detecting thepresence of 151P3D4 mRNA in the cell. Methods for the detection ofparticular mRNAs in cells are well known and include, for example,hybridization assays using complementary DNA probes (such as in situhybridization using labeled 151P3D4 riboprobes, Northern blot andrelated techniques) and various nucleic acid amplification assays (suchas RT-PCR using complementary primers specific for 151P3D4, and otheramplification type detection methods, such as, for example, branchedDNA, SISBA, TMA and the like). Alternatively, an assay for identifying acell that expresses a 151P3D4 gene comprises detecting the presence of151P3D4-related protein in the cell or secreted by the cell. Variousmethods for the detection of proteins are well known in the art and areemployed for the detection of 151P3D4-related proteins and cells thatexpress 151P3D4-related proteins.

[0244] 151P3D4 expression analysis is also useful as a tool foridentifying and evaluating agents that modulate 151P3D4 gene expression.For example, 151P3D4 expression is significantly upregulated in prostatecancer, and is expressed in cancers of the tissues listed in Table I.Identification of a molecule or biological agent that inhibits 151P3D4expression or over-expression in cancer cells is of therapeutic value.For example, such an agent can be identified by using a screen thatquantifies 151P3D4 expression by RT-PCR, nucleic acid hybridization orantibody binding.

[0245] VIII.) Methods for Monitoring the Status of 151P3D4-Related Genesand Their Products

[0246] Oncogenesis is known to be a multistep process where cellulargrowth becomes progressively dysregulated and cells progress from anormal physiological state to precancerous and then cancerous states(see, e.g., Alers et al., Lab Invest. 77(5): 437-438 (1997) and Isaacset al., Cancer Surv. 23: 19-32 (1995). In this context, examining abiological sample for evidence of dysregulated cell growth (such asaberrant 151P3D4 expression in cancers) allows for early detection ofsuch aberrant physiology, before a pathologic state such as cancer hasprogressed to a stage that therapeutic options are more limited and orthe prognosis is worse. In such examinations, the status of 151P3D4 in abiological sample of interest can be compared, for example, to thestatus of 151P3D4 in a corresponding normal sample (e.g. a sample fromthat individual or alternatively another individual that is not affectedby a pathology). An alteration in the status of 151P3D4 in thebiological sample (as compared to the normal sample) provides evidenceof dysregulated cellular growth. In addition to using a biologicalsample that is not affected by a pathology as a normal sample, one canalso use a predetermined normative value such as a predetermined normallevel of mRNA expression (see, e.g., Grever et al., J. Comp. Neurol.Dec. 9, 1996; 376(2): 306-14 and U.S. Pat. No. 5,837,501) to compare151P3D4 status in a sample.

[0247] The term “status” in this context is used according to its artaccepted meaning and refers to the condition or state of a gene and itsproducts. Typically, skilled artisans use a number of parameters toevaluate the condition or state of a gene and its products. Theseinclude, but are not limited to the location of expressed gene products(including the location of 151P3D4 expressing cells) as well as thelevel, and biological activity of expressed gene products (such as151P3D4 mRNA, polynucleotides and polypeptides). Typically, analteration in the status of 151P3D4 comprises a change in the locationof 151P3D4 and/or 151P3D4 express increase in 151P3D4 mRNA and/orprotein expression.

[0248] 151P3D4 status in a sample can be analyzed by a number of meanswell known in the art, including without limitation, immunohistochemicalanalysis, in situ hybridization, RT-PCR analysis on laser capturemicro-dissected samples, Western blot analysis, and tissue arrayanalysis. Typical protocols for evaluating the status of a 151P3D4 geneand gene products are found, for example in Ausubel et al. eds., 1995,Current Protocols In Molecular Biology, Units 2 (Northern Blotting), 4(Southern Blotting), 15 (Immunoblotting) and 18 (PCR Analysis). Thus,the status of 151P3D4 in a biological sample is evaluated by variousmethods utilized by skilled artisans including, but not limited togenomic Southern analysis (to examine, for example perturbations in a151P3D4 gene), Northern analysis and/or PCR analysis of 151P3D4 mRNA (toexamine, for example alterations in the polynucleotide sequences orexpression levels of 151P3D4 mRNAs), and, Western and/orimmunohistochemical analysis (to examine, for example alterations inpolypeptide sequences, alterations in polypeptide localization within asample, alterations in expression levels of 151P3D4 proteins and/orassociations of 151P3D4 proteins with polypeptide binding partners).Detectable 151P3D4 polynucleotides include, for example, a 151P3D4 geneor fragment thereof, 151P3D4 mRNA, alternative splice variants, 151P3D4mRNAs, and recombinant DNA or RNA molecules containing a 151P3D4polynucleotide.

[0249] The expression profile of 151P3D4 makes it a diagnostic markerfor local and/or metastasized disease, and provides information on thegrowth or oncogenic potential of a biological sample. In particular, thestatus of 151P3D4 provides information useful for predictingsusceptibility to particular disease stages, progression, and/or tumoraggressiveness. The invention provides methods and assays fordetermining 151P3D4 status and diagnosing cancers that express 151P3D4,such as cancers of the tissues listed in Table I. For example, because151P3D4 mRNA is so highly expressed in prostate and other cancersrelative to normal prostate tissue, assays that evaluate the levels of151P3D4 mRNA transcripts or proteins in a biological sample can be usedto diagnose a disease associated with 151P3D4 dysregulation, and canprovide prognostic information useful in defining appropriatetherapeutic options.

[0250] The expression status of 151P3D4 provides information includingthe presence, stage and location of dysplastic, precancerous andcancerous cells, predicting susceptibility to various stages of disease,and/or for gauging tumor aggressiveness. Moreover, the expressionprofile makes it useful as an imaging reagent for metastasized disease.Consequently, an aspect of the invention is directed to the variousmolecular prognostic and diagnostic methods for examining the status of151P3D4 in biological samples such as those from individuals sufferingfrom, or suspected of suffering from a pathology characterized bydysregulated cellular growth, such as cancer.

[0251] As described above, the status of 151P3D4 in a biological samplecan be examined by a number of well-known procedures in the art. Forexample, the status of 151P3D4 in a biological sample taken from aspecific location in the body can be examined by evaluating the samplefor the presence or absence of 151P3D4 expressing cells (e.g. those thatexpress 151P3D4 mRNAs or proteins). This examination can provideevidence of dysregulated cellular growth, for example, when151P3D4-expressing cells are found in a biological sample that does notnormally contain such cells (such as a lymph node), because suchalterations in the status of 151P3D4 in a biological sample are oftenassociated with dysregulated cellular growth. Specifically, oneindicator of dysregulated cellular growth is the metastases of cancercells from an organ of origin (such as the prostate) to a different areaof the body (such as a lymph node). In this context, evidence ofdysregulated cellular growth is important for example because occultlymph node metastases can be detected in a substantial proportion ofpatients with prostate cancer, and such metastases are associated withknown predictors of disease progression (see, e.g., Murphy et al.,Prostate 42(4): 315-317 (2000);Su et al., Semin. Surg. Oncol. 18(1):17-28 (2000) and Freeman et al., J Urol August 1995 154(2 Pt 1):474-8).

[0252] In one aspect, the invention provides methods for monitoring151P3D4 gene products by determining the status of 151P3D4 gene productsexpressed by cells from an individual suspected of having a diseaseassociated with dysregulated cell growth (such as hyperplasia or cancer)and then comparing the status so determined to the status of 151P3D4gene products in a corresponding normal sample. The presence of aberrant151P3D4 gene products in the test sample relative to the normal sampleprovides an indication of the presence of dysregulated cell growthwithin the cells of the individual.

[0253] In another aspect, the invention provides assays useful indetermining the presence of cancer in an individual, comprisingdetecting a significant increase in 151P3D4 mRNA or protein expressionin a test cell or tissue sample relative to expression levels in thecorresponding normal cell or tissue. The presence of 151P3D4 mRNA can,for example, be evaluated in tissues including but not limited to thoselisted in Table I. The presence of significant 151P3D4 expression in anyof these tissues is useful to indicate the emergence, presence and/orseverity of a cancer, since the corresponding normal tissues do notexpress 151P3D4 mRNA or express it at lower levels.

[0254] In a related embodiment, 151P3D4 status is determined at theprotein level rather than at the nucleic acid level. For example, such amethod comprises determining the level of 151P3D4 protein expressed bycells in a test tissue sample and comparing the level so determined tothe level of 151P3D4 expressed in a corresponding normal sample. In oneembodiment, the presence of 151P3D4 protein is evaluated, for example,using immunohistochemical methods. 151P3D4 antibodies or bindingpartners capable of detecting 151P3D4 protein, expression are used in avariety of assay formats well known in the art for this purpose.

[0255] In a further embodiment, one can evaluate the status of 151P3D4nucleotide and amino acid sequences in a biological sample in order toidentify perturbations in the structure of these molecules. Theseperturbations can include insertions, deletions, substitutions and thelike. Such evaluations are useful because perturbations in thenucleotide and amino acid sequences are observed in a large number ofproteins associated with a growth dysregulated phenotype (see, e.g.,Marrogi et al., 1999, J. Cutan. Pathol. 26(8):369-378). For example, amutation in the sequence of 151P3D4 may be indicative of the presence orpromotion of a tumor. Such assays therefore have diagnostic andpredictive value where a mutation in 151P3D4 indicates a potential lossof function or increase in tumor growth.

[0256] A wide variety of assays for observing perturbations innucleotide and amino acid sequences are well known in the art. Forexample, the size and structure of nucleic acid or amino acid sequencesof 151P3D4 gene products are observed by the Northern, Southern,Western, PCR and DNA sequencing protocols discussed herein. In addition,other methods for observing perturbations in nucleotide and amino acidsequences such as single strand conformation polymorphism analysis arewell known in the art (see, e.g., U.S. Pat. Nos. 5,382,510 issued Sep.7, 1999 and 5,952,170 issued Jan. 17, 1995).

[0257] Additionally, one can examine the methylation status of a 151P3D4gene in a biological sample. Aberrant demethylation and/orhypermethylation of CpG islands in gene 5′ regulatory regions frequentlyoccurs in immortalized and transformed cells, and can result in alteredexpression of various genes. For example, promoter hypermethylation ofthe pi-class glutathione S-transferase (a protein expressed in normalprostate but not expressed in >90% of prostate carcinomas) appears topermanently silence transcription of this gene and is the mostfrequently detected genomic alteration in prostate carcinomas (De Marzoet al., Am. J. Pathol. 155(6): 1985-1992 (1999)). In addition, thisalteration is present in at least 70% of cases of high-grade prostaticintraepithelial neoplasia (PIN) (Brooks et al., Cancer Epidemiol.Biomarkers Prev., 1998, 7:531-536). In another example, expression ofthe LAGE-I tumor specific gene (which is not expressed in normalprostate but is expressed in 25-50% of prostate cancers) is induced bydeoxy-azacytidine in lymphoblastoid cells, suggesting that tumoralexpression is due to demethylation (Lethe et al., Int. J. Cancer 76(6):903-908 (1998)). A variety of assays for examining methylation status ofa gene are well known in the art. For example, one can utilize, inSouthern hybridization approaches, methylation-sensitive restrictionenzymes that cannot cleave sequences that contain methylated CpG sitesto assess the methylation status of CpG islands. In addition, MSP(methylation specific PCR) can rapidly profile the methylation status ofall the CpG sites present in a CpG island of a given gene. Thisprocedure involves initial modification of DNA by sodium bisulfite(which will convert all unmethylated cytosines to uracil) followed byamplification using primers specific for methylated versus unmethylatedDNA. Protocols involving methylation interference can also be found forexample in Current Protocols In Molecular Biology, Unit 12, Frederick M.Ausubel et al. eds., 1995.

[0258] Gene amplification is an additional method for assessing thestatus of 151P3D4. Gene amplification is measured in a sample directly,for example, by conventional Southern blotting or Northern blotting toquantitate the transcription of mRNA (Thomas, 1980, Proc. Natl. Acad.Sci. USA, 77:5201-5205), dot blotting (DNA analysis), or in situhybridization, using an appropriately labeled probe, based on thesequences provided herein. Alternatively, antibodies are employed thatrecognize specific duplexes, including DNA duplexes, RNA duplexes, andDNA-RNA hybrid duplexes or DNA-protein duplexes. The antibodies in turnare labeled and the assay carried out where the duplex is bound to asurface, so that upon the formation of duplex on the surface, thepresence of antibody bound to the duplex can be detected.

[0259] Biopsied tissue or peripheral blood can be conveniently assayedfor the presence of cancer cells using for example, Northern, dot blotor RT-PCR analysis to detect 151P3D4 expression. The presence of RT-PCRamplifiable 151P3D4 mRNA provides an indication of the presence ofcancer. RT-PCR assays are well known in the art. RT-PCR detection assaysfor tumor cells in peripheral blood are currently being evaluated foruse in the diagnosis and management of a number of human solid tumors.In the prostate cancer field, these include RT-PCR assays for thedetection of cells expressing PSA and PSM (Verkaik et al., 1997, Urol.Res. 25:373-384; Ghossein et al., 1995, J. Clin. Oncol. 13:1195-2000;Heston et al., 1995, Clin. Chem 41:1687-1688).

[0260] A further aspect of the invention is an assessment of thesusceptibility that an individual has for developing cancer. In oneembodiment, a method for predicting susceptibility to cancer comprisesdetecting 151P3D4 mRNA or 151P3D4 protein in a tissue sample, itspresence indicating susceptibility to cancer, wherein the degree of151P3D4 mRNA expression correlates to the degree of susceptibility. In aspecific embodiment, the presence of 151P3D4 in prostate or other tissueis examined, with the presence of 151P3D4 in the sample providing anindication of prostate cancer susceptibility (or the emergence orexistence of a prostate tumor). Similarly, one can evaluate theintegrity 151P3D4 nucleotide and amino acid sequences in a biologicalsample, in order to identify perturbations in the structure of thesemolecules such as insertions, deletions, substitutions and the like. Thepresence of one or more perturbations in 151P3D4 gene products in thesample is an indication of cancer susceptibility (or the emergence orexistence of a tumor).

[0261] The invention also comprises methods for gauging tumoraggressiveness. In one embodiment, a method for gauging aggressivenessof a tumor comprises determining the level of 151P3D4 mRNA or 151P3D4protein expressed by tumor cells, comparing the level so determined tothe level of 151P3D4 mRNA or 151P3D4 protein expressed in acorresponding normal tissue taken from the same individual or a normaltissue reference sample, wherein the degree of 151P3D4 mRNA or 151P3D4protein expression in the tumor sample relative to the normal sampleindicates the degree of aggressiveness. In a specific embodiment,aggressiveness of a tumor is evaluated by determining the extent towhich 151P3D4 is expressed in the tumor cells, with higher expressionlevels indicating more aggressive tumors. Another embodiment is theevaluation of the integrity of 151P3D4 nucleotide and amino acidsequences in a biological sample, in order to identify perturbations inthe structure of these molecules such as insertions, deletions,substitutions and the like. The presence of one or more perturbationsindicates more aggressive tumors.

[0262] Another embodiment of the invention is directed to methods forobserving the progression of a malignancy in an individual over time. Inone embodiment, methods for observing the progression of a malignancy inan individual over time comprise determining the level of 151P3D4 mRNAor 151P3D4 protein expressed by cells in a sample of the tumor,comparing the level so determined to the level of 151P3D4 mRNA or151P3D4 protein expressed in an equivalent tissue sample taken from thesame individual at a different time, wherein the degree of 151P3D4 mRNAor 151P3D4 protein expression in the tumor sample over time providesinformation on the progression of the cancer. In a specific embodiment,the progression of a cancer is evaluated by determining 151P3D4expression in the tumor cells over time, where increased expression overtime indicates a progression of the cancer. Also, one can evaluate theintegrity 151P3D4 nucleotide and amino acid sequences in a biologicalsample in order to identify perturbations in the structure of thesemolecules such as insertions, deletions, substitutions and the like,where the presence of one or more perturbations indicates a progressionof the cancer.

[0263] The above diagnostic approaches can be combined with any one of awide variety of prognostic and diagnostic protocols known in the art.For example, another embodiment of the invention is directed to methodsfor observing a coincidence between the expression of 151P3D4 gene and151P3D4 gene products (or perturbations in 151P3D4 gene and 151P3D4 geneproducts) and a factor that is associated with malignancy, as a meansfor diagnosing and prognosticating the status of a tissue sample. A widevariety of factors associated with malignancy can be utilized, such asthe expression of genes associated with malignancy (e.g. PSA, PSCA andPSM expression for prostate cancer etc.) as well as gross cytologicalobservations (see, e.g., Bocking et al., 1984, Anal. Quant. Cytol.6(2):74-88; Epstein, 1995, Hum. Pathol. 26(2):223-9; Thorson et al.,199, Mod. Pathol. 11(6):543-51; Baisden et al., 1999, Am. J. Surg.Pathol. 23(8):918-24). Methods for observing a coincidence between theexpression of 151P3D4 gene and 151P3D4 gene products (or perturbationsin 151P3D4 gene and 151P3D4 gene products) and another factor that isassociated with malignancy are useful, for example, because the presenceof a set of specific factors that coincide with disease providesinformation crucial for diagnosing and prognosticating the status of atissue sample.

[0264] In one embodiment, methods for observing a coincidence betweenthe expression of 151P3D4 gene and 151P3D4 gene products (orperturbations in 151P3D4 gene and 151P3D4 gene products) and anotherfactor associated with malignancy entails detecting the overexpressionof 151P3D4 mRNA or protein in a tissue sample, detecting theoverexpression of PSA mRNA or protein in a tissue sample (or PSCA or PSMexpression), and observing a coincidence of 151P3D4 mRNA or protein andPSA mRNA or protein overexpression (or PSCA or PSM expression). In aspecific embodiment, the expression of 151P3D4 and PSA mRNA in prostatetissue is examined, where the coincidence of 151P3D4 and PSA mRNAoverexpression in the sample indicates the existence of prostate cancer,prostate cancer susceptibility or the emergence or status of a prostatetumor.

[0265] Methods for detecting and quantifying the expression of 151P3D4mRNA or protein are described herein, and standard nucleic acid andprotein detection and quantification technologies are well known in theart. Standard methods for the detection and quantification of 151P3D4mRNA include in situ hybridization using labeled 151P3D4 riboprobes,Northern blot and related techniques using 151P3D4 polynucleotideprobes, RT-PCR analysis using primers specific for 151P3D4, and otheramplification type detection methods, such as, for example, branchedDNA, SISBA, TMA and the like. In a specific embodiment,semi-quantitative RT-PCR is used to detect and quantify 151P3D4 mRNAexpression. Any number of primers capable of amplifying 151P3D4 can beused for this purpose, including but not limited to the various primersets specifically described herein. In a specific embodiment, polyclonalor monoclonal antibodies specifically reactive with the wild-type151P3D4 protein can be used in an immunohistochemical assay of biopsiedtissue.

[0266] IX.) Identification of Molecules that Interact with 151P3D4

[0267] The 151P3D4 protein and nucleic acid sequences disclosed hereinallow a skilled artisan to identify proteins, small molecules and otheragents that interact with 151P3D4, as well as pathways activated by151P3D4 via any one of a variety of art accepted protocols. For example,one can utilize one of the so-called interaction trap systems (alsoreferred to as the “two-hybrid assay”). In such systems, moleculesinteract and reconstitute a transcription factor which directsexpression of a reporter gene, whereupon the expression of the reportergene is assayed. Other systems identify protein-protein interactions invivo through reconstitution of a eukaryotic transcriptional activator,see, e.g., U.S. Pat. Nos. 5,955,280 issued Sep. 21, 1999, 5,925,523issued Jul. 20, 1999, 5,846,722 issued Dec. 8, 1998 and 6,004,746 issuedDec. 21, 1999. Algorithms are also available in the art for genome-basedpredictions of protein function (see, e.g., Marcotte, et al., Nature402: Nov. 4, 1999, 83-86).

[0268] Alternatively one can screen peptide libraries to identifymolecules that interact with 151P3D4 protein sequences. In such methods,peptides that bind to 151P3D4 are identified by screening libraries thatencode a random or controlled collection of amino acids. Peptidesencoded by the libraries are expressed as fusion proteins ofbacteriophage coat proteins, the bacteriophage particles are thenscreened against the 151P3D4 protein(s).

[0269] Accordingly, peptides having a wide variety of uses, such astherapeutic, prognostic or diagnostic reagents, are thus identifiedwithout any prior information on the structure of the expected ligand orreceptor molecule. Typical peptide libraries and screening methods thatcan be used to identify molecules that interact with 151P3D4 proteinsequences are disclosed for example in U.S. Pat. Nos. 5,723,286 issuedMar. 3, 1998 and 5,733,731 issued Mar. 31, 1998.

[0270] Alternatively, cell lines that express 151P3D4 are used toidentify protein-protein interactions mediated by 151P3D4. Suchinteractions can be examined using immunoprecipitation techniques (see,e.g., Hamilton B. J., et al. Biochem. Biophys. Res. Commun. 1999,261:646-51). 151P3D4 protein can be immunoprecipitated from151P3D4-expressing cell lines using anti-151P3D4 antibodies.Alternatively, antibodies against His-tag can be used in a cell lineengineered to express fusions of 151P3D4 and a His-tag (vectorsmentioned above). The immunoprecipitated complex can be examined forprotein association by procedures such as Western blotting,³⁵S-methionine labeling of proteins, protein microsequencing, silverstaining and two-dimensional gel electrophoresis.

[0271] Small molecules and ligands that interact with 151P3D4 can beidentified through related embodiments of such screening assays. Forexample, small molecules can be identified that interfere with proteinfunction, including molecules that interfere with 151P3D4's ability tomediate phosphorylation and de-phosphorylation, interaction with DNA orRNA molecules as an indication of regulation of cell cycles, secondmessenger signaling or tumorigenesis. Similarly, small molecules thatmodulate 151P3D4-related ion channel, protein pump, or cellcommunication functions are identified and used to treat patients thathave a cancer that expresses 151P3D4 (see, e.g., Hille, B., IonicChannels of Excitable Membranes 2^(nd) Ed., Sinauer Assoc., Sunderland,Mass., 1992). Moreover, ligands that regulate 151P3D4 function can beidentified based on their ability to bind 151P3D4 and activate areporter construct. Typical methods are discussed for example in U.S.Pat. No. 5,928,868 issued Jul. 27, 1999, and include methods for forminghybrid ligands in which at least one ligand is a small molecule. In anillustrative embodiment, cells engineered to express a fusion protein of151P3D4 and a DNA-binding protein are used to co-express a fusionprotein of a hybrid ligand/small molecule and a cDNA librarytranscriptional activator protein. The cells further contain a reportergene, the expression of which is conditioned on the proximity of thefirst and second fusion proteins to each other, an event that occursonly if the hybrid ligand binds to target sites on both hybrid proteins.Those cells that express the reporter gene are selected and the unknownsmall molecule or the unknown ligand is identified. This method providesa means of identifying modulators which activate or inhibit 151P3D4.

[0272] An embodiment of this invention comprises a method of screeningfor a molecule that interacts with a 151P3D4 amino acid sequence shownin FIG. 2 or FIG. 3, comprising the steps of contacting a population ofmolecules with a 151P3D4 amino acid sequence, allowing the population ofmolecules and the 151P3D4 amino acid sequence to interact underconditions that facilitate an interaction, determining the presence of amolecule that interacts with the 151P3D4 amino acid sequence, and thenseparating molecules that do not interact with the 151P3D4 amino acidsequence from molecules that do. In a specific. embodiment, the methodfurther comprises purifying, characterizing and identifying a moleculethat interacts with the 151P3D4 amino acid sequence. The identifiedmolecule can be used to modulate a function performed by 151P3D4. In apreferred embodiment, the 151P3D4 amino acid sequence is contacted witha library of peptides.

[0273] X.) Therapeutic Methods and Compositions

[0274] The identification of 151P3D4 as a protein that is normallyexpressed in a restricted set of tissues, but which is also expressed inprostate and other cancers, opens a number of therapeutic approaches tothe treatment of such cancers. As contemplated herein, 151P3D4 functionsas a transcription factor involved in activating tumor-promoting genesor repressing genes that block tumorigenesis.

[0275] Accordingly, therapeutic approaches that inhibit the activity ofa 151P3D4 protein are useful for patients suffering from a cancer thatexpresses 151P3D4. These therapeutic approaches generally fall into twoclasses. One class comprises various methods for inhibiting the bindingor association of a 151P3D4 protein with its binding partner or withother proteins. Another class comprises a variety of methods forinhibiting the transcription of a 151P3D4 gene or translation of 151P3D4mRNA.

[0276] X.A.) Anti-Cancer Vaccines

[0277] The invention provides cancer vaccines comprising a151P3D4-related protein or 151P3D4-related nucleic acid. In view of theexpression of 151P3D4, cancer vaccines prevent and/or treat151P3D4-expressing cancers with minimal or no effects on non-targettissues. The use of a tumor antigen in a vaccine that generates humoraland/or cell-mediated immune responses as anti-cancer therapy is wellknown in the art and has been employed in prostate cancer using humanPSMA and rodent PAP immunogens (Hodge et al., 1995, Int. J. Cancer63:231-237; Fong et al., 1997, J. Immunol. 159:3113-3117).

[0278] Such methods can be readily practiced by employing a151P3D4-related protein, or a 151P3D4-encoding nucleic acid molecule andrecombinant vectors capable of expressing and presenting the 151P3D4immunogen (which typically comprises a number of antibody or T cellepitopes). Skilled artisans understand that a wide variety of vaccinesystems for delivery of immunoreactive epitopes are known in the art(see, e.g., Heryln et al., Ann Med February 1999 31(1):66-78; Maruyamaet al., Cancer Immunol Immunother June 2000 49(3):123-32) Briefly, suchmethods of generating an immune response (e.g. humoral and/orcell-mediated) in a mammal, comprise the steps of: exposing the mammal'simmune system to an immunoreactive epitope (e.g. an epitope present in a151P3D4 protein shown in FIG. 3 or analog or homolog thereof) so thatthe mammal generates an immune response that is specific for thatepitope (e.g. generates antibodies that specifically recognize thatepitope). In a preferred method, a 151P3D4 immunogen contains abiological motif, see e.g., Tables V-XVIII and XXII-LI, or a peptide ofa size range from 151P3D4 indicated in FIG. 5, FIG. 6, FIG. 7, FIG. 8,and FIG. 9.

[0279] The entire 151P3D4 protein, immunogenic regions or epitopesthereof can be combined and delivered by various means. Such vaccinecompositions can include, for example, lipopeptides (e.g., Vitiello, A.et al., J. Clin. Invest. 95:341, 1995), peptide compositionsencapsulated in poly(DL-lactide-co-glycolide) (“PLG”) microspheres (see,e.g., Eldridge, et al., Molec. Immunol. 28:287-294, 1991: Alonso et al.,Vaccine 12:299-306, 1994; Jones et al., Vaccine 13:675-681, 1995),peptide compositions contained in immune stimulating complexes (ISCOMS)(see, e.g., Takahashi et al., Nature 344:873-875, 1990; Hu et al., ClinExp Immunol. 113:235-243, 1998), multiple antigen peptide systems (MAPs)(see e.g., Tam, J. P., Proc. Natl. Acad. Sci. U.S.A. 85:5409-5413, 1988;Tam, J. P., J. Immunol. Methods 196:17-32, 1996), peptides formulated asmultivalent peptides; peptides for use in ballistic delivery systems,typically crystallized peptides, viral delivery vectors (Perkus, M. E.et al., In: Concepts in vaccine development, Kaufmann, S. H. E., ed., p.379, 1996; Chakrabarti, S. et al., Nature 320:535, 1986; Hu, S. L. etal., Nature 320:537, 1986; Kieny, M.-P. et al., AIDS Bio/Technology4:790, 1986; Top, F. H. et al., J. Infect. Dis. 124:148, 1971; Chanda,P. K. et al., Virology 175:535, 1990), particles of viral or syntheticorigin (e.g., Kofler, N. et al., J. Immunol. Methods. 192:25, 1996;Eldridge, J. H. et al., Sem. Hematol. 30:16, 1993; Falo, L. D., Jr. etal., Nature Med. 7:649, 1995), adjuvants (Warren, H. S., Vogel, F. R.,and Chedid, L. A. Annu. Rev. Immunol. 4:369, 1986; Gupta, R. K. et al.,Vaccine 11:293, 1993), liposomes (Reddy, R. et al., J. Immunol.148:1585, 1992; Rock, K. L., Immunol. Today 17:131, 1996), or, naked orparticle absorbed cDNA (Ulmer, J. B. et al., Science 259:1745, 1993;Robinson, H. L., Hunt, L. A., and Webster, R. G., Vaccine 11:957, 1993;Shiver, J. W. et al., In: Concepts in vaccine development, Kaufmann, S.H. E., ed., p. 423, 1996; Cease, K. B., and Berzofsky, J. A., Annu. Rev.Immunol. 12:923, 1994 and Eldridge, J. H. et al., Sem. Hematol. 30:16,1993). Toxin-targeted delivery technologies, also known as receptormediated targeting, such as those of Avant Immunotherapeutics, Inc.(Needham, Mass.) may also be used.

[0280] In patients with 151P3D4-associated cancer, the vaccinecompositions of the invention can also be used in conjunction with othertreatments used for cancer, e.g., surgery, chemotherapy, drug therapies,radiation therapies, etc. including use in combination with immuneadjuvants such as IL-2, IL-12, GM-CSF, and the like.

[0281] Cellular Vaccines:

[0282] CTL epitopes can be determined using specific algorithms toidentify peptides within 151P3D4 protein that bind corresponding HLAalleles (see e.g., Table IV; Epimer™ and Epimatrix™, Brown University(URL www.brown.edu/Research/TB-HIV_Lab/epimatrix/epimatrix.html); and,BIMAS, (URL bimas.dcrt.nih.gov/; SYFPEITHI at URLsyfpeithi.bmi-heidelberg.com/). In a preferred embodiment, a 151P3D4immunogen contains one or more amino acid sequences identified usingtechniques well known in the art, such as the sequences shown in TablesV-XVIII and XXII-LI or a peptide of 8, 9, 10 or 11 amino acids specifiedby an HLA Class I motig/supermotif (e.g., Table IV (A), Table IV (D), orTable IV (E)) and/or a peptide of at least 9 amino acids that comprisesan HLA Class II motif/supermotif (e.g., Table IV (B) or Table IV (C)).As is appreciated in the art, the HLA Class I binding groove isessentially closed ended so that peptides of only a particular sizerange can fit into the groove and be bound, generally HLA Class Iepitopes are 8, 9, 10, or 11 amino acids long. In contrast, the HLAClass II binding groove is essentially open ended; therefore a peptideof about 9 or more amino acids can be bound by an HLA Class II molecule.Due to the binding groove differences between HLA Class I and II, HLAClass I motifs are length specific, i.e., position two of a Class Imotif is the second amino acid in an amino to carboxyl direction of thepeptide. The amino acid positions in a Class II motif are relative onlyto each other, not the overall peptide, i.e., additional amino acids canbe attached to the amino and/or carboxyl termini of a motif-bearingsequence. HLA Class II epitopes are often 9, 10, 11, 12, 13, 14, 15, 16,17, 18, 19, 20, 21, 22, 23, 24, or 25 amino acids long, or longer than25 amino acids.

[0283] Antibody-Based Vaccines

[0284] A wide variety of methods for generating an immune response in amammal are known in the art (for example as the first step in thegeneration of hybridomas). Methods of generating an immune response in amammal comprise exposing the mammal's immune system to an immunogenicepitope on a protein (e.g. a 151P3D4 protein) so that an immune responseis generated. A typical embodiment consists of a method for generatingan immune response to 151P3D4 in a host, by contacting the host with asufficient amount of at least one 151P3D4 B cell or cytotoxic T-cellepitope or analog thereof; and at least one periodic interval thereafterre-contacting the host with the 151P3D4 B cell or cytotoxic T-cellepitope or analog thereof. A specific embodiment consists of a method ofgenerating an immune response against a 151P3D4-related protein or aman-made multiepitopic peptide comprising: administering 151P3D4immunogen (e.g. a 151P3D4 protein or a peptide fragment thereof, a151P3D4 fusion protein or analog etc.) in a vaccine preparation to ahuman or another mammal. Typically, such vaccine preparations furthercontain a suitable adjuvant (see, e.g., U.S. Pat. No. 6,146,635) or auniversal helper epitope such as a PADRE™ peptide (Epimmune Inc., SanDiego, Calif; see, e.g., Alexander et al., J. Immunol. 2000 164(3);164(3): 1625-1633; Alexander et al., Immunity 1994 1(9): 751-761 andAlexander et al., Immunol. Res. 1998 18(2): 79-92). An alternativemethod comprises generating an immune response in an individual againsta 151P3D4 immunogen by: administering in vivo to muscle or skin of theindividual's body a DNA molecule that comprises a DNA sequence thatencodes a 151P3D4 immunogen, the DNA sequence operatively linked toregulatory sequences which control the expression of the DNA sequence;wherein the DNA molecule is taken up by cells, the DNA sequence isexpressed in the cells and an immune response is generated against theimmunogen (see, e.g., U.S. Pat. No. 5,962,428). Optionally a geneticvaccine facilitator such as anionic lipids; saponins; lectins;estrogenic compounds; hydroxylated lower alkyls; dimethyl sulfoxide; andurea is also administered. In addition, an antiidiotypic antibody can beadministered that mimics 151P3D4, in order to generate a response to thetarget antigen.

[0285] Nucleic Acid Vaccines:

[0286] Vaccine compositions of the invention include nucleicacid-mediated modalities. DNA or RNA that encode protein(s) of theinvention can be administered to a patient. Genetic immunization methodscan be employed to generate prophylactic or therapeutic humoral andcellular immune responses directed against cancer cells expressing151P3D4. Constructs comprising DNA encoding a 151P3D4-relatedprotein/immunogen and appropriate regulatory sequences can be injecteddirectly into muscle or skin of an individual, such that the cells ofthe muscle or skin take-up the construct and express the encoded 151P3D4protein/immunogen. Alternatively, a vaccine comprises a 151P3D4-relatedprotein. Expression of the 151P3D4-related protein immunogen results inthe generation of prophylactic or therapeutic humoral and cellularimmunity against cells that bear a 151P3D4 protein. Various prophylacticand therapeutic genetic immunization techniques known in the art can beused (for review, see information and references published at Internetaddress www.genweb.com). Nucleic acid-based delivery is described, forinstance, in Wolff et. al., Science 247:1465 (1990) as well as U.S. Pat.Nos. 5,580,859; 5,589,466; 5,804,566; 5,739,118; 5,736,524; 5,679,647;WO 98/04720. Examples of DNA-based delivery technologies include “nakedDNA”, facilitated (bupivicaine, polymers, peptide-mediated) delivery,cationic lipid complexes, and particle-mediated (“gene gun”) orpressure-mediated delivery (see, e.g., U.S. Pat. No. 5,922,687).

[0287] For therapeutic or prophylactic immunization purposes, proteinsof the invention can be expressed via viral or bacterial vectors.Various viral gene delivery systems that can be used in the practice ofthe invention include, but are not limited to, vaccinia, fowlpox,canarypox, adenovirus, influenza, poliovirus, adeno-associated virus,lentivirus, and sindbis virus (see, e.g., Restifo, 1996, Curr. Opin.Immunol. 8:658-663; Tsang et al. J. Natl. Cancer Inst. 87:982-990(1995)). Non-viral delivery systems can also be employed by introducingnaked DNA encoding a 151P3D4-related protein into the patient (e.g.,intramuscularly or intradermally) to induce an anti-tumor response.

[0288] Vaccinia virus is used, for example, as a vector to expressnucleotide sequences that encode the peptides of the invention. Uponintroduction into a host, the recombinant vaccinia virus expresses theprotein immunogenic peptide, and thereby elicits a host immune response.Vaccinia vectors and methods useful in immunization protocols aredescribed in, e.g., U.S. Pat. No. 4,722,848. Another vector is BCG(Bacille Calmette Guerin). BCG vectors are described in Stover et al.,Nature 351:456-460(1991). A wide variety of other vectors useful fortherapeutic administration or immunization of the peptides of theinvention, e.g. adeno and adeno-associated virus vectors, retroviralvectors, Salmonella typhi vectors, detoxified anthrax toxin vectors, andthe like, will be apparent to those skilled in the art from thedescription herein.

[0289] Thus, gene delivery systems are used to deliver a 151P3D4-relatednucleic acid molecule. In one embodiment, the full-length human 151P3D4cDNA is employed. In another embodiment, 151P3D4 nucleic acid moleculesencoding specific cytotoxic T lymphocyte (CTL) and/or antibody epitopesare employed.

[0290] Ex Vivo Vaccines

[0291] Various ex vivo strategies can also be employed to generate animmune response. One approach involves the use of antigen presentingcells (APCs) such as dendritic cells (DC) to present 151P3D4 antigen toa patient's immune system. Dendritic cells express MHC class I and IImolecules, B7 co-stimulator, and IL-12, and are thus highly specializedantigen presenting cells. In prostate cancer, autologous dendritic cellspulsed with peptides of the prostate-specific membrane antigen (PSMA)are being used in a Phase I clinical trial to stimulate prostate cancerpatients' immune systems (Tjoa et al., 1996, Prostate 28:65-69; Murphyet al., 1996, Prostate 29:371-380). Thus, dendritic cells can be used topresent 151P3D4 peptides to T cells in the context. of MHC class I or IImolecules. In one embodiment, autologous dendritic cells are pulsed with151P3D4 peptides capable of binding to MHC class I and/or class IImolecules. In another embodiment, dendritic cells are pulsed with thecomplete 151P3D4 protein. Yet another embodiment involves engineeringthe overexpression of a 151P3D4 gene in dendritic cells using variousimplementing vectors known in the art, such as adenovirus (Arthur etal., 1997, Cancer Gene Ther. 4:17-25), retrovirus (Henderson et al.,1996, Cancer Res. 56:3763-3770), lentivirus, adeno-associated virus, DNAtransfection (Ribas et al., 1997, Cancer Res. 57:2865-2869), ortumor-derived RNA transfection (Ashley et al., 1997, J. Exp. Med.186:1177-1182). Cells that express 151P3D4 can also be engineered toexpress immune modulators, such as GM-CSF, and used as immunizingagents.

[0292] X.B.) 151P3D4 as a Target for Antibody-Based Therapy

[0293] 151P3D4 is an attractive target for antibody-based therapeuticstrategies. A number of antibody strategies are known in the art fortargeting both extracellular and intracellular molecules (see, e.g.,complement and ADCC mediated killing as well as the use of intrabodies).Because 151P3D4 is expressed by cancer cells of various lineagesrelative to corresponding normal cells, systemic administration of151P3D4-immunoreactive compositions are prepared that exhibit excellentsensitivity without toxic, non-specific and/or non-target effects causedby binding of the immunoreactive composition to non-target organs andtissues. Antibodies specifically reactive with domains of 151P3D4 areuseful to treat 151P3D4-expressing cancers systemically, either asconjugates with a toxin or therapeutic agent, or as naked antibodiescapable of inhibiting cell proliferation or function.

[0294] 151P3D4 antibodies can be introduced into a patient such that theantibody binds to 151P3D4 and modulates a function, such as aninteraction with a binding partner, and consequently mediatesdestruction of the tumor cells and/or inhibits the growth of the tumorcells. Mechanisms by which such antibodies exert a therapeutic effectcan include complement-mediated cytolysis, antibody-dependent cellularcytotoxicity, modulation of the physiological function of 151P3D4,inhibition of ligand binding or signal transduction pathways, modulationof tumor cell differentiation, alteration of tumor angiogenesis factorprofiles, and/or apoptosis.

[0295] Those skilled in the art understand that antibodies can be usedto specifically target and bind immunogenic molecules such as animmunogenic region of a 151P3D4 sequence shown in FIG. 2 or FIG. 3. Inaddition, skilled artisans understand that it is routine to conjugateantibodies to cytotoxic agents (see, e.g., Slevers et al. Blood 93:113678-3684 (Jun. 1, 1999)). When cytotoxic and/or therapeutic agents aredelivered directly to cells, such as by conjugating them to antibodiesspecific for a molecule expressed by that cell (e.g. 151P3D4), thecytotoxic agent will exert its known biological effect (i.e.cytotoxicity) on those cells.

[0296] A wide variety of compositions and methods for usingantibody-cytotoxic agent conjugates to kill cells are known in the art.In the context of cancers, typical methods entail administering to ananimal having a tumor a biologically effective amount of a conjugatecomprising a selected cytotoxic and/or therapeutic agent linked to atargeting agent (e.g. an anti-151P3D4 antibody) that binds to a marker(e.g. 151P3D4) expressed, accessible to binding or localized on the cellsurfaces. A typical embodiment is a method of delivering a cytotoxicand/or therapeutic agent to a cell expressing 151P3D4, comprisingconjugating the cytotoxic agent to an antibody that immunospecificallybinds to a 151P3D4 epitope, and, exposing the cell to the antibody-agentconjugate. Another illustrative embodiment is a method of treating anindividual suspected of suffering from metastasized cancer, comprising astep of administering parenterally to said individual a pharmaceuticalcomposition comprising a therapeutically effective amount of an antibodyconjugated to a cytotoxic and/or therapeutic agent.

[0297] Cancer immunotherapy using anti-151P3D4 antibodies can be done inaccordance with various approaches that have been successfully employedin the treatment of other types of cancer, including but not limited tocolon cancer (Arlen et al., 1998, Crit. Rev. Immunol. 18:133-138),multiple myeloma (Ozaki et al., 1997, Blood 90:3179-3186, Tsunenari etal., 1997, Blood 90:2437-2444), gastric cancer (Kasprzyk et al., 1992,Cancer Res. 52:2771-2776), B-cell lymphoma (Funakoshi et al., 1996, J.Immunother. Emphasis Tumor Immunol. 19:93-101), leukemia (Zhong et al.,1996, Leuk. Res. 20:581-589), colorectal cancer (Moun et al., 1994,Cancer Res. 54:6160-6166; Velders et al., 1995, Cancer Res.55:4398-4403), and breast cancer (Shepard et al., 1991, J. Clin.Immunol. 11:117-127). Some therapeutic approaches involve conjugation ofnaked antibody to a toxin or radioisotope, such as the conjugation ofY⁹¹ or I¹³¹ to anti-CD20 antibodies (e.g., Zevalin™, IDECPharmaceuticals Corp. or Bexxar™, Coulter Pharmaceuticals), while othersinvolve co-administration of antibodies and other therapeutic agents,such as Herceptin™ (trastuzumab) with paclitaxel (Genentech, Inc.). Theantibodies can be conjugated to a therapeutic agent. To treat prostatecancer, for example, 151P3D4 antibodies can be administered inconjunction with radiation, chemotherapy or hormone ablation. Also,antibodies can be conjugated to a toxin such as calicheamicin (e.g.,Mylotarg™, Wyeth-Ayerst, Madison, N.J., a recombinant humanized IgG₄kappa antibody conjugated to antitumor antibiotic calicheamicin) or amaytansinoid (e.g., taxane-based Tumor-Activated Prodrug, TAP, platform,ImmunoGen, Cambridge, Mass., also see e.g., U.S. Pat. No. 5,416,064).

[0298] Although 151P3D4 antibody therapy is useful for all stages ofcancer, antibody therapy can be particularly appropriate in advanced ormetastatic cancers. Treatment with the antibody therapy of the inventionis indicated for patients who have received one or more rounds ofchemotherapy. Alternatively, antibody therapy of the invention iscombined with a chemotherapeutic or radiation regimen for patients whohave not received chemotherapeutic treatment. Additionally, antibodytherapy can enable the use of reduced dosages of concomitantchemotherapy, particularly for patients who do not tolerate the toxicityof the chemotherapeutic agent very well. Fan et al. (Cancer Res.53:4637-4642, 1993), Prewett et al. (International J. of Onco.9:217-224, 1996), and Hancock et al. (Cancer Res. 51:4575-4580, 1991)describe the use of various antibodies together with chemotherapeuticagents.

[0299] Although 151P3D4 antibody therapy is useful for all stages ofcancer, antibody therapy can be particularly appropriate in advanced ormetastatic cancers. Treatment with the antibody therapy of the inventionis indicated for patients who have received one or more rounds ofchemotherapy. Alternatively, antibody therapy of the invention iscombined with a chemotherapeutic or radiation regimen for patients whohave not received chemotherapeutic treatment. Additionally, antibodytherapy can enable the use of reduced dosages of concomitantchemotherapy, particularly for patients who do not tolerate the toxicityof the chemotherapeutic agent very well.

[0300] Cancer patients can be evaluated for the presence and level of151P3D4 expression, preferably using immunohistochemical assessments oftumor tissue, quantitative 151P3D4 imaging, or other techniques thatreliably indicate the presence and degree of 151P3D4 expression.Immunohistochemical analysis of tumor biopsies or surgical specimens ispreferred for this purpose. Methods for immunohistochemical analysis oftumor tissues are well known in the art.

[0301] Anti-151P3D4 monoclonal antibodies that treat prostate and othercancers include those that initiate a potent immune response against thetumor or those that are directly cytotoxic. In this regard, anti-151P3D4monoclonal antibodies (mAbs) can elicit tumor cell lysis by eithercomplement-mediated or antibody-dependent cell cytotoxicity (ADCC)mechanisms, both of which require an intact Fc portion of theimmunoglobulin molecule for interaction with effector cell Fc receptorsites on complement proteins. In addition, anti-151P3D4 mAbs that exerta direct biological effect on tumor growth are useful to treat cancersthat express 151P3D4. Mechanisms by which directly cytotoxic mAbs actinclude: inhibition of cell growth, modulation of cellulardifferentiation, modulation of tumor angiogenesis factor profiles, andthe induction of apoptosis. The mechanism(s) by which a particularanti-151P3D4 mAb exerts an anti-tumor effect is evaluated using anynumber of in vitro assays that evaluate cell death such as ADCC, ADMMC,complement-mediated cell lysis, and so forth, as is generally known inthe art.

[0302] In some patients, the use of murine or other non-human monoclonalantibodies, or human/mouse chimeric mAbs can induce moderate to strongimmune responses against the non-human antibody. This can result inclearance of the antibody from circulation and reduced efficacy. In themost severe cases, such an immune response can lead to the extensiveformation of immune complexes which, potentially, can cause renalfailure. Accordingly, preferred monoclonal antibodies used in thetherapeutic methods of the invention are those that are either fullyhuman or humanized and that bind specifically to the target 151P3D4antigen with high affinity but exhibit low or no antigenicity in thepatient.

[0303] Therapeutic methods of the invention contemplate theadministration of single anti-151P3D4 mAbs as well as combinations, orcocktails, of different mAbs. Such mAb cocktails can have certainadvantages inasmuch as they contain mAbs that target different epitopes,exploit different effector mechanisms or combine directly cytotoxic mAbswith mAbs that rely on immune effector functionality. Such mAbs incombination can exhibit synergistic therapeutic effects. In addition,anti-151P3D4 mAbs can be administered concomitantly with othertherapeutic modalities, including but not limited to variouschemotherapeutic agents, androgen-blockers, immune modulators (e.g.,IL-2, GM-CSF), surgery or radiation. The anti-151P3D4 mAbs areadministered in their “naked” or unconjugated form, or can have atherapeutic agent(s) conjugated to them.

[0304] Anti-151P3D4 antibody formulations are administered via any routecapable of delivering the antibodies to a tumor cell. Routes ofadministration include, but are not limited to, intravenous,intraperitoneal, intramuscular, intratumor, intradermal, and the like.Treatment generally involves repeated administration of the anti-151P3D4antibody preparation, via an acceptable route of administration such asintravenous injection (IV), typically at a dose in the range of about0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9,10, 15, 20, or 25 mg/kg body weight. In general, doses in the range of10-1000 mg mAb per week are effective and well tolerated.

[0305] Based on clinical experience with the Herceptin™ mAb in thetreatment of metastatic breast cancer, an initial loading dose ofapproximately 4 mg/kg patient body weight IV, followed by weekly dosesof about 2 mg/kg IV of the anti-151P3D4 mAb preparation represents anacceptable dosing regimen. Preferably, the initial loading dose isadministered as a 90 minute or longer infusion. The periodic maintenancedose is administered as a 30 minute or longer infusion, provided theinitial dose was well tolerated. As appreciated by those of skill in theart, various factors can influence the ideal dose regimen in aparticular case. Such factors include, for example, the binding affinityand half life of the Ab or mAbs used, the degree of 151P3D4 expressionin the patient, the extent of circulating shed 151P3D4 antigen, thedesired steady-state antibody concentration level, frequency oftreatment, and the influence of chemotherapeutic or other agents used incombination with the treatment method of the invention, as well as thehealth status of a particular patient.

[0306] Optionally, patients should be evaluated for the levels of151P3D4 in a given sample (e.g. the levels of circulating 151P3D4antigen and/or 151P3D4 expressing cells) in order to assist in thedetermination of the most effective dosing regimen, etc. Suchevaluations are also used for monitoring purposes throughout therapy,and are useful to gauge therapeutic success in combination with theevaluation of other parameters (for example, urine cytology and/orImmunoCyt levels in bladder cancer therapy, or by analogy, serum PSAlevels in prostate cancer therapy).

[0307] Anti-idiotypic anti-151P3D4 antibodies can also be used inanti-cancer therapy as a vaccine for inducing an immune response tocells expressing a 151P3D4-related protein. In particular, thegeneration of anti-idiotypic antibodies is well known in the art; thismethodology can readily be adapted to generate anti-idiotypicanti-151P3D4 antibodies that mimic an epitope on a 151P3D4-relatedprotein (see, for example, Wagner et al., 1997, Hybridoma 16: 33-40;Foon et al., 1995, J. Clin. Invest. 96:334-342; Herlyn et al., 1996,Cancer Immunol. Immunother. 43:65-76). Such an anti-idiotypic antibodycan be used in cancer vaccine strategies.

[0308] X.C.) 151P3D4 as a Target for Cellular Immune Responses

[0309] Vaccines and methods of preparing vaccines that contain animmunogenically effective amount of one or more HLA-binding peptides asdescribed herein are further embodiments of the invention. Furthermore,vaccines in accordance with the invention encompass compositions of oneor more of the claimed peptides. A peptide can be present in a vaccineindividually. Alternatively, the peptide can exist as a homopolymercomprising multiple copies of the same peptide, or as a heteropolymer ofvarious peptides. Polymers have the advantage of increased immunologicalreaction and, where different peptide epitopes are used to make up thepolymer, the additional ability to induce antibodies and/or CTLs thatreact with different antigenic determinants of the pathogenic organismor tumor-related peptide targeted for an immune response. Thecomposition can be a naturally occurring region of an antigen or can beprepared, e.g., recombinantly or by chemical synthesis.

[0310] Carriers that can be used with vaccines of the invention are wellknown in the art, and include, e.g., thyroglobulin, albumins such ashuman serum albumin, tetanus toxoid, polyamino acids such as polyL-lysine, poly L-glutamic acid, influenza, hepatitis B virus coreprotein, and the like. The vaccines can contain a physiologicallytolerable (i.e., acceptable) diluent such as water, or saline,preferably phosphate buffered saline. The vaccines also typicallyinclude an adjuvant. Adjuvants such as incomplete Freund's adjuvant,aluminum phosphate, aluminum hydroxide, or alum are examples ofmaterials well known in the art. Additionally, as disclosed herein, CTLresponses can be primed by conjugating peptides of the invention tolipids, such as tripalmitoyl-S-glycerylcysteinlyseryl-serine (P₃CSS).Moreover, an adjuvant such as a syntheticcytosine-phosphorothiolated-guanine-containing (CpG) oligonucleotideshas been found to increase CTL responses 10- to 100-fold. (see, e.g.Davila and Celis, J. Immunol. 165:539-547 (2000))

[0311] Upon immunization with a peptide composition in accordance withthe invention, via injection, aerosol, oral, transdermal, transmucosal,intrapleural, intrathecal, or other suitable routes, the immune systemof the host responds to the vaccine by producing large amounts of CTLsand/or HTLs specific for the desired antigen. Consequently, the hostbecomes at least partially immune to later development of cells thatexpress or overexpress 151P3D4 antigen, or derives at least sometherapeutic benefit when the antigen was tumor-associated.

[0312] In some embodiments, it may be desirable to combine the class Ipeptide components with components that induce or facilitateneutralizing antibody and or helper T cell responses directed to thetarget antigen. A preferred embodiment of such a composition comprisesclass I and class II epitopes in accordance with the invention. Analternative embodiment of such a composition comprises a class I and/orclass II epitope in accordance with the invention, along with a crossreactive HTL epitope such as PADRE™ (Epimmune, San Diego, Calif.)molecule (described eg., in U.S. Pat. No. 5,736,142).

[0313] A vaccine of the invention can also include antigen-presentingcells (APC), such as dendritic cells (DC), as a vehicle to presentpeptides of the invention. Vaccine compositions can be created in vitro,following dendritic cell mobilization and harvesting, whereby loading ofdendritic cells occurs in vitro. For example, dendritic cells aretransfected, e.g., with a minigene in accordance with the invention, orare pulsed with peptides. The dendritic cell can then be administered toa patient to elicit immune responses in vivo. Vaccine compositions,either DNA- or peptide-based, can also be administered in vivo incombination with dendritic cell mobilization whereby loading ofdendritic cells occurs in vivo.

[0314] Preferably, the following principles are utilized when selectingan array of epitopes for inclusion in a polyepitopic composition for usein a vaccine, or for selecting discrete epitopes to be included in avaccine and/or to be encoded by nucleic acids such as a minigene. It ispreferred that each of the following principles be balanced in order tomake the selection. The multiple epitopes to be incorporated in a givenvaccine composition may be, but need not be, contiguous in sequence inthe native antigen from which the epitopes are derived.

[0315] 1.) Epitopes are selected which, upon administration, mimicimmune responses that have been observed to be correlated with tumorclearance. For HLA Class I this includes 3-4 epitopes that come from atleast one tumor associated antigen (TAA). For HLA Class II a similarrationale is employed; again 3-4 epitopes are selected from at least oneTAA (see, e.g., Rosenberg et al., Science 278:1447-1450). Epitopes fromone TAA may be used in combination with epitopes from one or moreadditional TAAs to produce a vaccine that targets tumors with varyingexpression patterns of frequently-expressed TAAs.

[0316] 2.) Epitopes are selected that have the requisite bindingaffinity established to be correlated with immunogenicity: for HLA ClassI an IC₅₀ of 500 nM or less, often 200 nM or less; and for Class II anIC₅₀ of 1000 nM or less.

[0317] 3.) Sufficient supermotif bearing-peptides, or a sufficient arrayof allele-specific motif-bearing peptides, are selected to give broadpopulation coverage. For example, it is preferable to have at least 80%population coverage. A Monte Carlo analysis, a statistical evaluationknown in the art, can be employed to assess the breadth, or redundancyof, population coverage.

[0318] 4.) When selecting epitopes from cancer-related antigens it isoften useful to select analogs because the patient may have developedtolerance to the native epitope.

[0319] 5.) Of particular relevance are epitopes referred to as “nestedepitopes.” Nested epitopes occur where at least two epitopes overlap ina given peptide sequence. A nested peptide sequence can comprise B cell,HLA class I and/or HLA class II epitopes. When providing nestedepitopes, a general objective is to provide the greatest number ofepitopes per sequence. Thus, an aspect is to avoid providing a peptidethat is any longer than the amino terminus of the amino terminal epitopeand the carboxyl terminus of the carboxyl terminal epitope in thepeptide. When providing a multi-epitopic sequence, such as a sequencecomprising nested epitopes, it is generally important to screen thesequence in order to insure that it does not have pathological or otherdeleterious biological properties.

[0320] 6.) If a polyepitopic protein is created, or when creating aminigene, an objective is to generate the smallest peptide thatencompasses the epitopes of interest. This principle is similar, if notthe same as that employed when selecting a peptide comprising nestedepitopes. However, with an artificial polyepitopic peptide, the sizeminimization objective is balanced against the need to integrate anyspacer sequences between epitopes in the polyepitopic protein. Spaceramino acid residues can, for example, be introduced to avoid junctionalepitopes (an epitope recognized by the immune system, not present in thetarget antigen, and only created by the man-made juxtaposition ofepitopes), or to facilitate cleavage between epitopes and therebyenhance epitope presentation. Junctional epitopes are generally to beavoided because the recipient may generate an immune response to thatnon-native epitope. Of particular concern is a junctional epitope thatis a “dominant epitope.” A dominant epitope may lead to such a zealousresponse that immune responses to other epitopes are diminished orsuppressed.

[0321] 7.) Where the sequences of multiple variants of the same targetprotein are present, potential peptide epitopes can also be selected onthe basis of their conservancy. For example, a criterion for conservancymay define that the entire sequence of an HLA class I binding peptide orthe entire 9-mer core of a class II binding peptide be conserved in adesignated percentage of the sequences evaluated for a specific proteinantigen.

[0322] X.C.1. Minigene Vaccines

[0323] A number of different approaches are available which allowsimultaneous delivery of multiple epitopes. Nucleic acids encoding thepeptides of the invention are a particularly useful embodiment of theinvention. Epitopes for inclusion in a minigene are preferably selectedaccording to the guidelines set forth in the previous section. Apreferred means of administering nucleic acids encoding the peptides ofthe invention uses minigene constructs encoding a peptide comprising oneor multiple epitopes of the invention.

[0324] The use of multi-epitope minigenes is described below and in,Ishioka et al., J. Immunol. 162:3915-3925, 1999; An, L. and Whitton, J.L., J. Virol. 71:2292, 1997; Thomson, S. A. et al., J. Immunol. 157:822,1996; Whitton, J. L. et al., J. Virol. 67:348, 1993; Hanke, R. et al.,Vaccine 16:426, 1998. For example, a multi-epitope DNA plasmid encodingsupermotif- and/or motif-bearing epitopes derived 151P3D4, the PADRE®universal helper T cell epitope or multiple HTL epitopes from 151P3D4(see e.g., Tables V-XVIII and XXII to LI), and an endoplasmicreticulum-translocating signal sequence can be engineered. A vaccine mayalso comprise epitopes that are derived from other TAAs.

[0325] The immunogenicity of a multi-epitopic minigene can be confirmedin transgenic mice to evaluate the magnitude of CTL induction responsesagainst the epitopes tested. Further, the immunogenicity of DNA-encodedepitopes in vivo can be correlated with the in vitro responses ofspecific CTL lines against target cells transfected with the DNAplasmid. Thus, these experiments can show that the minigene serves toboth: 1.) generate a CTL response and 2.) that the induced CTLsrecognized cells expressing the encoded epitopes.

[0326] For example, to create a DNA sequence encoding the selectedepitopes (minigene) for expression in human cells, the amino acidsequences of the epitopes may be reverse translated. A human codon usagetable can be used to guide the codon choice for each amino acid. Theseepitope-encoding DNA sequences may be directly adjoined, so that whentranslated, a continuous polypeptide sequence is created. To optimizeexpression and/or immunogenicity, additional elements can beincorporated into the minigene design. Examples of amino acid sequencesthat can be reverse translated and included in the minigene sequenceinclude: HLA class I epitopes, HLA class II epitopes, antibody epitopes,a ubiquitination signal sequence, and/or an endoplasmic reticulumtargeting signal. In addition, HLA presentation of CTL and HTL epitopesmay be improved by including synthetic (e.g. poly-alanine) ornaturally-occurring flanking sequences adjacent to the CTL or HTLepitopes; these larger peptides comprising the epitope(s) are within thescope of the invention.

[0327] The minigene sequence may be converted to DNA by assemblingoligonucleotides that encode the plus and minus strands of the minigene.Overlapping oligonucleotides (30-100 bases long) may be synthesized,phosphorylated, purified and annealed under appropriate conditions usingwell known techniques. The ends of the oligonucleotides can be joined,for example, using T4 DNA ligase. This synthetic minigene, encoding theepitope polypeptide, can then be cloned into a desired expressionvector.

[0328] Standard regulatory sequences well known to those of skill in theart are preferably included in the vector to ensure expression in thetarget cells. Several vector elements are desirable: a promoter with adownstream cloning site for minigene insertion; a polyadenylation signalfor efficient transcription termination; an E. coli origin ofreplication; and an E. coli selectable marker (e.g. ampicillin orkanamycin resistance). Numerous promoters can be used for this purpose,e.g., the human cytomegalovirus (hCMV) promoter. See, e.g., U.S. Pat.Nos. 5,580,859 and 5,589,466 for other suitable promoter sequences.

[0329] Additional vector modifications may be desired to optimizeminigene expression and immunogenicity. In some cases, introns arerequired for efficient gene expression, and one or more synthetic ornaturally-occurring introns could be incorporated into the transcribedregion of the minigene. The inclusion of mRNA stabilization sequencesand sequences for replication in mammalian cells may also be consideredfor increasing minigene expression.

[0330] Once an expression vector is selected, the minigene is clonedinto the polylinker region downstream of the promoter. This plasmid istransformed into an appropriate E. coli strain, and DNA is preparedusing standard techniques. The orientation and DNA sequence of theminigene, as well as all other elements included in the vector, areconfirmed using restriction mapping and DNA sequence analysis. Bacterialcells harboring the correct plasmid can be stored as a master cell bankand a working cell bank.

[0331] In addition, immunostimulatory sequences (ISSs or CpGs) appear toplay a role in the immunogenicity of DNA vaccines. These sequences maybe included in the vector, outside the minigene coding sequence, ifdesired to enhance immunogenicity.

[0332] In some embodiments, a bi-cistronic expression vector whichallows production of both the minigene-encoded epitopes and a secondprotein (included to enhance or decrease immunogenicity) can be used.Examples of proteins or polypeptides that could beneficially enhance theimmune response if co-expressed include cytokines (e.g., IL-2, IL-12,GM-CSF), cytokine-inducing molecules (e.g., LeIF), costimulatorymolecules, or for HTL responses, pan-DR binding proteins (PADRE™,Epimmune, San Diego, Calif.). Helper (HTL) epitopes can be joined tointracellular targeting signals and expressed separately from expressedCTL epitopes; this allows direction of the HTL epitopes to a cellcompartment different than that of the CTL epitopes. If required, thiscould facilitate more efficient entry of HTL epitopes into the HLA classII pathway, thereby improving HTL induction. In contrast to HTL or CTLinduction, specifically decreasing the immune response by co-expressionof immunosuppressive molecules (e.g. TGFβ,) may be beneficial in certaindiseases.

[0333] Therapeutic quantities of plasmid DNA can be produced forexample, by fermentation in E. coli, followed by purification. Aliquotsfrom the working cell bank are used to inoculate growth medium, andgrown to. saturation in shaker flasks or a bioreactor according towell-known techniques. Plasmid DNA can be purified using standardbioseparation technologies such as solid phase anion-exchange resinssupplied by QIAGEN, Inc. (Valencia, Calif.). If required, supercoiledDNA can be isolated from the open circular and linear forms using gelelectrophoresis or other methods.

[0334] Purified plasmid DNA can be prepared for injection using avariety of formulations. The simplest of these is reconstitution oflyophilized DNA in sterile phosphate-buffer saline (PBS). This approach,known as “naked DNA,” is currently being used for intramuscular (IM)administration in clinical trials. To maximize the immunotherapeuticeffects of minigene DNA vaccines, an alternative method for formulatingpurified plasmid DNA may be desirable. A variety of methods have beendescribed, and new techniques may become available. Cationic lipids,glycolipids, and fusogenic liposomes can also be used in the formulation(see, e.g., as described by WO 93/24640; Mannino & Gould-Fogerite,BioTechniques 6(7): 682 (1988); U.S. Pat No. 5,279,833; WO 91/06309; andFelgner, et al., Proc. Nat'l Acad. Sci. USA 84:7413 (1987). In addition,peptides and compounds referred to collectively as protective,interactive, non-condensing compounds (PINC) could also be complexed topurified plasmid DNA to influence variables such as stability,intramuscular dispersion, or trafficking to specific organs or celltypes.

[0335] Target cell sensitization can be used as a functional assay forexpression and HLA class I presentation of minigene-encoded CTLepitopes. For example, the plasmid DNA is introduced into a mammaliancell line that is suitable as a target for standard CTL chromium releaseassays. The transfection method used will be dependent on the finalformulation. Electroporation can be used for “naked” DNA, whereascationic lipids allow direct in vitro transfection. A plasmid expressinggreen fluorescent protein (GFP) can be co-transfected to allowenrichment of transfected cells using fluorescence activated cellsorting (FACS). These cells are then chromium-51 (⁵¹Cr) labeled and usedas target cells for epitope-specific CTL lines; cytolysis, detected by⁵¹Cr release, indicates both production of, and HLA presentation of,minigene-encoded CTL epitopes. Expression of HTL epitopes may beevaluated in an analogous manner using assays to assess HTL activity.

[0336] In vivo immunogenicity is a second approach for functionaltesting of minigene DNA formulations. Transgenic mice expressingappropriate human HLA proteins are immunized with the DNA product. Thedose and route of administration are formulation dependent (e.g., IM forDNA in PBS, intraperitoneal (i.p.) for lipid-complexed DNA). Twenty-onedays after immunization, splenocytes are harvested and restimulated forone week in the presence of peptides encoding each epitope being tested.Thereafter, for CTL effector cells, assays are conducted for cytolysisof peptide-loaded, ⁵¹Cr-labeled target cells using standard techniques.Lysis of target cells that were sensitized by HLA loaded with peptideepitopes, corresponding to minigene-encoded epitopes, demonstrates DNAvaccine function for in vivo induction of CTLs. Immunogenicity of HTLepitopes is confirmed in transgenic mice in an analogous manner.

[0337] Alternatively, the nucleic acids can be administered usingballistic delivery as described, for instance, in U.S. Pat. No.5,204,253. Using this technique, particles comprised solely of DNA areadministered. In a further alternative embodiment, DNA can be adhered toparticles, such as gold particles.

[0338] Minigenes can also be delivered using other bacterial or viraldelivery systems well known in the art, e.g., an expression constructencoding epitopes of the invention can be incorporated into a viralvector such as vaccinia.

[0339] X.C.2. Combinations of CTL Peptides with Helper Peptides

[0340] Vaccine compositions comprising CTL peptides of the invention canbe modified, e.g., analoged, to provide desired attributes, such asimproved serum half life, broadened population coverage or enhancedimmunogenicity.

[0341] For instance, the ability of a peptide to induce CTL activity canbe enhanced by linking the peptide to a sequence which contains at leastone epitope that is capable of inducing a T helper cell response.Although a CTL peptide can be directly linked to a T helper peptide,often CTL epitope/HTL epitope conjugates are linked by a spacermolecule. The spacer is typically comprised of relatively small, neutralmolecules, such as amino acids or amino acid mimetics, which aresubstantially uncharged under physiological conditions. The spacers aretypically selected from, e.g., Ala, Gly, or other neutral spacers ofnonpolar amino acids or neutral polar amino acids. It will be understoodthat the optionally present spacer need not be comprised of the sameresidues and thus may be a hetero- or homo-oligomer. When present, thespacer will usually be at least one or two residues, more usually threeto six residues and sometimes 10 or more residues. The CTL peptideepitope can be linked to the T helper peptide epitope either directly orvia a spacer either at the amino or carboxy terminus of the CTL peptide.The amino terminus of either the immunogenic peptide or the T helperpeptide may be acylated.

[0342] In certain embodiments, the T helper peptide is one that isrecognized by T helper cells present in a majority of a geneticallydiverse population. This can be accomplished by selecting peptides thatbind to many, most, or all of the HLA class II molecules. Examples ofsuch amino acid bind many HLA Class II molecules include sequences fromantigens such as tetanus toxoid at positions 830-843 (QYIKANSKFIGITE;SEQ ID NO:______), Plasmodium falciparum circumsporozoite (CS) proteinat positions 378-398 (DIEKKIAKMEKASSVFNVVNS; SEQ ID NO:______), andStreptococcus 18kD protein at positions 116-131 (GAVDSILGGVATYGAA; SEQID NO:______). Other examples include peptides bearing a DR 1-4-7supermotif, or either of the DR3 motifs.

[0343] Alternatively, it is possible to prepare synthetic peptidescapable of stimulating T helper lymphocytes, in a loosely HLA-restrictedfashion, using amino acid sequences not found in nature (see, e.g., PCTpublication WO 95/07707). These synthetic compounds calledPan-DR-binding epitopes (e.g., PADRE™, Epimmune, Inc., San Diego,Calif.) are designed to most preferably bind most HLA-DR (human HLAclass II) molecules. For instance, a pan-DR-binding epitope peptidehaving the formula: aKXVAAWTLKAAa (SEQ ID NO:______), where “X” iseither cyclohexylalanine, phenylalanine, or tyrosine, and a is eitherD-alanine or L-alanine, has been found to bind to most HLA-DR alleles,and to stimulate the response of T helper lymphocytes from mostindividuals, regardless of their HLA type. An alternative of a pan-DRbinding epitope comprises all “L” natural amino acids and can beprovided in the form of nucleic acids that encode the epitope.

[0344] HTL peptide epitopes can also be modified to alter theirbiological properties. For example, they can be modified to includeD-amino acids to increase their resistance to proteases and thus extendtheir serum half life, or they can be conjugated to other molecules suchas lipids, proteins, carbohydrates, and the like to increase theirbiological activity. For example, a T helper peptide can be conjugatedto one or more palmitic acid chains at either the amino or carboxyltermini.

[0345] X.C.3. Combinations of CTL Peptides with T Cell Priming Agents

[0346] In some embodiments it may be desirable to include in thepharmaceutical compositions of the invention at least one componentwhich primes B lymphocytes or T lymphocytes. Lipids have been identifiedas agents capable of priming CTL in vivo. For example, palmitic acidresidues can be attached to the ε- and α-amino groups of a lysineresidue and then linked, e.g., via one or more linking residues such asGly, Gly-Gly-, Ser, Ser-Ser, or the like, to an immunogenic peptide. Thelipidated peptide can then be administered either directly in a micelleor particle, incorporated into a liposome, or emulsified in an adjuvant,e.g., incomplete Freund's adjuvant. In a preferred embodiment, aparticularly effective immunogenic composition comprises palmitic acidattached to ε- and α-amino groups of Lys, which is attached via linkage,e.g., Ser-Ser, to the amino terminus of the immunogenic peptide.

[0347] As another example of lipid priming of CTL responses, E. colilipoproteins, such as tripalmitoyl-S-glycerylcysteinlyseryl-serine(P₃CSS) can be used to prime virus specific CTL when covalently attachedto an appropriate peptide (see, e.g., Deres, et al., Nature 342:561,1989). Peptides of the invention can be coupled to P₃CSS, for example,and the lipopeptide administered to an individual to specifically primean immune response to the target antigen. Moreover, because theinduction of neutralizing antibodies can also be primed withP₃CSS-conjugated epitopes, two such compositions can be combined to moreeffectively elicit both humoral and cell-mediated responses.

[0348] X.C.4. Vaccine Compositions Comprising DC Pulsed with CTL and/orHTL Peptides

[0349] An embodiment of a vaccine composition in accordance with theinvention comprises ex vivo administration of a cocktail ofepitope-bearing peptides to PBMC, or isolated DC therefrom, from thepatient's blood. A pharmaceutical to facilitate harvesting of DC can beused, such as Progenipoietin™ (Pharmacia-Monsanto, St. Louis, Mo.) orGM-CSF/IL-4. After pulsing the DC with peptides and prior to reinfusioninto patients, the DC are washed to remove unbound peptides. In thisembodiment, a vaccine comprises peptide-pulsed DCs which present thepulsed peptide epitopes complexed with HLA molecules on their surfaces.

[0350] The DC can be pulsed ex vivo with a cocktail of peptides, some ofwhich stimulate CTL responses to 151P3D4. Optionally, a helper T cell(HTL) peptide, such as a natural or artificial loosely restricted HLAClass II peptide, can be included to facilitate the CTL response. Thus,a vaccine in accordance with the invention is used to treat a cancerwhich expresses or overexpresses 151P3D4.

[0351] X.D. Adoptive Immunotherapy

[0352] Antigenic 151P3D4-related peptides are used to elicit a CTLand/or HTL response ex vivo, as well. The resulting CTL or HTL cells,can be used to treat tumors in patients that do not respond to otherconventional forms of therapy, or will not respond to a therapeuticvaccine peptide or nucleic acid in accordance with the invention. Exvivo CTL or HTL responses to a particular antigen are induced byincubating in tissue culture the patient's, or genetically compatible,CTL or HTL precursor cells together with a source of antigen-presentingcells (APC), such as dendritic cells, and the appropriate immunogenicpeptide. After an appropriate incubation time (typically about 7-28days), in which the precursor cells are activated and expanded intoeffector cells, the cells are infused back into the patient, where theywill destroy (CTL) or facilitate destruction (HTL) of their specifictarget cell (e.g., a tumor cell). Transfected dendritic cells may alsobe used as antigen presenting cells.

[0353] X.E. Administration of Vaccines for Therapeutic or ProphylacticPurposes

[0354] Pharmaceutical and vaccine compositions of the invention aretypically used to treat and/or prevent a cancer that expresses oroverexpresses 151P3D4. In therapeutic applications, peptide and/ornucleic acid compositions are administered to a patient in an amountsufficient to elicit an effective B cell, CTL and/or HTL response to theantigen and to cure or at least partially arrest or slow symptoms and/orcomplications. An amount adequate to accomplish this is defined as“therapeutically effective dose.” Amounts effective for this use willdepend on, e.g., the particular composition administered, the manner ofadministration, the stage and severity of the disease being treated, theweight and general state of health of the patient, and the judgment ofthe prescribing physician.

[0355] For pharmaceutical compositions, the immunogenic peptides of theinvention, or DNA encoding them, are generally administered to anindividual already bearing a tumor that expresses 151P3D4. The peptidesor DNA encoding them can be administered individually or as fusions ofone or more peptide sequences. Patients can be treated with theimmunogenic peptides separately or in conjunction with other treatments,such as surgery, as appropriate.

[0356] For therapeutic use, administration should generally begin at thefirst diagnosis of 151P3D4-associated cancer. This is followed byboosting doses until at least symptoms are substantially abated and fora period thereafter. The embodiment of the vaccine composition (ie.,including, but not limited to embodiments such as peptide cocktails,polyepitopic polypeptides, minigenes, or TAA-specific CTLs or pulseddendritic cells) delivered to the patient may vary according to thestage of the disease or the patient's health status. For example, in apatient with a tumor that expresses 151P3D4, a vaccine comprising151P3D4-specific CTL may be more efficacious in killing tumor cells inpatient with advanced disease than alternative embodiments.

[0357] It is generally important to provide an amount of the peptideepitope delivered by a mode of administration sufficient to effectivelystimulate a cytotoxic T cell response; compositions which stimulatehelper T cell responses can also be given in accordance with thisembodiment of the invention.

[0358] The dosage for an initial therapeutic immunization generallyoccurs in a unit dosage range where the lower value is about 1, 5, 50,500, or 1,000 μg and the higher value is about 10,000; 20,000; 30,000;or 50,000 μg. Dosage values for a human typically range from about 500μg to about 50,000 μg per 70 kilogram patient. Boosting dosages ofbetween about 1.0 μg to about 50,000 μg of peptide pursuant to aboosting regimen over weeks to months may be administered depending uponthe patient's response and condition as determined by measuring thespecific activity of CTL and HTL obtained from the patient's blood.Administration should continue until at least clinical symptoms orlaboratory tests indicate that the neoplasia, has been eliminated orreduced and for a period thereafter. The dosages, routes ofadministration, and dose schedules are adjusted in accordance withmethodologies known in the art.

[0359] In certain embodiments, the peptides and compositions of thepresent invention are employed in serious disease states, that is,life-threatening or potentially life threatening situations. In suchcases, as a result of the minimal amounts of extraneous substances andthe relative nontoxic nature of the peptides in preferred compositionsof the invention, it is possible and may be felt desirable by thetreating physician to administer substantial excesses of these peptidecompositions relative to these stated dosage amounts.

[0360] The vaccine compositions of the invention can also be used purelyas prophylactic agents. Generally the dosage for an initial prophylacticimmunization generally occurs in a unit dosage range where the lowervalue is about 1, 5, 50, 500, or 1000 μg and the higher value is about10,000; 20,000; 30,000; or 50,000 μg. Dosage values for a humantypically range from about 500 μg to about 50,000 μg per 70 kilogrampatient. This is followed by boosting dosages of between about 1.0 μg toabout 50,000 μg of peptide administered at defined intervals from aboutfour weeks to six months after the initial administration of vaccine.The immunogenicity of the vaccine can be assessed by measuring thespecific activity of CTL and HTL obtained from a sample of the patient'sblood.

[0361] The pharmaceutical compositions for therapeutic treatment areintended for parenteral, topical, oral, nasal, intrathecal, or local(e.g. as a cream or topical ointment) administration. Preferably, thepharmaceutical compositions are administered parentally, e.g.,intravenously, subcutaneously, intradermally, or intramuscularly. Thus,the invention provides compositions for parenteral administration whichcomprise a solution of the immunogenic peptides dissolved or suspendedin an acceptable carrier, preferably an aqueous carrier.

[0362] A variety of aqueous carriers may be used, e.g., water, bufferedwater, 0.8% saline, 0.3% glycine, hyaluronic acid and the like. Thesecompositions may be sterilized by conventional, well-known sterilizationtechniques, or may be sterile filtered. The resulting aqueous solutionsmay be packaged for use as is, or lyophilized, the lyophilizedpreparation being combined with a sterile solution prior toadministration.

[0363] The compositions may contain pharmaceutically acceptableauxiliary substances as required to approximate physiologicalconditions, such as pH-adjusting and buffering agents, tonicityadjusting agents, wetting agents, preservatives, and the like, forexample, sodium acetate, sodium lactate, sodium chloride, potassiumchloride, calcium chloride, sorbitan monolaurate, triethanolarnineoleate, etc.

[0364] The concentration of peptides of the invention in thepharmaceutical formulations can vary widely, i.e., from less than about0.1%, usually at or at least about 2% to as much as 20% to 50% or moreby weight, and will be selected primarily by fluid volumes, viscosities,etc., in accordance with the particular mode of administration selected.

[0365] A human unit dose form of a composition is typically included ina pharmaceutical composition that comprises a human unit dose of anacceptable carrier, in one embodiment an aqueous carrier, and isadministered in a volume/quantity that is known by those of skill in theart to be used for administration of such compositions to humans (see,e.g., Remington's Pharmaceutical Sciences, 17^(th) Edition, A. Gennaro,Editor, Mack Publishing Co., Easton, Pa., 1985). For example a peptidedose for initial immunization can be from about 1 to about 50,000 μg,generally 100-5,000 μg, for a 70 kg patient. For example, for nucleicacids an initial immunization may be performed using an expressionvector in the form of naked nucleic acid administered IM (or SC or ID)in the amounts of 0.5-5 mg at multiple sites. The nucleic acid (0.1 to1000 μg) can also be administered using a gene gun. Following anincubation period of 34 weeks, a booster dose is then administered. Thebooster can be recombinant fowlpox virus administered at a dose of 5-10⁷to 5×10⁹ pfu.

[0366] For antibodies, a treatment generally involves repeatedadministration of the anti-151P3D4 antibody preparation, via anacceptable route of administration such as intravenous injection (IV),typically at a dose in the range of about 0.1 to about 10 mg/kg bodyweight. In general, doses in the range of 10-500 mg mAb per week areeffective and well tolerated. Moreover, an initial loading dose ofapproximately 4 mg/kg patient body weight IV, followed by weekly dosesof about 2 mg/kg IV of the anti-151P3D4 mAb preparation represents anacceptable dosing regimen. As appreciated by those of skill in the art,various factors can influence the ideal dose in a particular case. Suchfactors include, for example, half life of a composition, the bindingaffinity of an Ab, the immunogenicity of a substance, the degree of151P3D4 expression in the patient, the extent of circulating shed151P3D4 antigen, the desired steady-state concentration level, frequencyof treatment, and the influence of chemotherapeutic or other agents usedin combination with the treatment method of the invention, as well asthe health status of a particular patient. Non-limiting preferred humanunit doses are, for example, 500 μg-1 mg, 1 mg-50 mg, 50 mg-100 mg, 100mg-200 mg, 200 mg-300 mg, 400 mg-500 mg, 500 mg-600 mg, 600 mg-700 mg,700 mg-800 mg, 800 mg-900 mg, 900 mg-1 g, or 1 mg-700 mg. In certainembodiments, the dose is in a range of 2-5 mg/kg body weight, e.g., withfollow on weekly doses of 1-3 mg/kg; 0.5 mg, 1, 2, 3, 4, 5, 6, 7, 8, 9,10 mg/kg body weight followed, e.g., in two, three or four weeks byweekly doses; 0.5-10 mg/kg body weight, e.g., followed in two, three orfour weeks by weekly doses; 225, 250, 275, 300, 325, 350, 375, 400 mg m²of body area weekly; 1-600 mg m² of body area weekly; 225-400 mg m² ofbody area weekly; these does can be followed by weekly doses for 2, 3,4, 5, 6, 7, 8, 9, 19, 11, 12 or more weeks.

[0367] In one embodiment, human unit dose forms of polynucleotidescomprise a suitable dosage range or effective amount that provides anytherapeutic effect. As appreciated by one of ordinary skill in the art atherapeutic effect depends on a number of factors, including thesequence of the polynucleotide, molecular weight of the polynucleotideand route of administration. Dosages are generally selected by thephysician or other health care professional in accordance with a varietyof parameters known in the art, such as severity of symptoms, history ofthe patient and the like. Generally, for a polynucleotide of about 20bases, a dosage range may be selected from, for example, anindependently selected lower limit such as about 0.1, 0.25, 0.5, 1, 2,5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400 or 500 mg/kgup to an independently selected upper limit, greater than the lowerlimit, of about 60, 80, 100, 200, 300, 400, 500, 750, 1000, 1500, 2000,3000, 4000, 5000, 6000, 7000, 8000, 9000 or 10,000 mg/kg. For example, adose may be about any of the following: 0.1 to 100 mg/kg, 0.1 to 50mg/kg, 0.1 to 25 mg/kg, 0.1 to 10 mg/kg, 1 to 500 mg/kg, 100 to 400mg/kg, 200 to 300 mg/kg, 1 to 100 mg/kg, 100 to 200 mg/kg, 300 to 400mg/kg, 400 to 500 mg/kg, 500 to 1000 mg/kg, 500 to 5000 mg/kg, or 500 to10,000 mg/kg. Generally, parenteral routes of administration may requirehigher doses of polynucleotide compared to more direct application tothe nucleotide to diseased tissue, as do polynucleotides of increasinglength.

[0368] In one embodiment, human unit dose forms of T-cells comprise asuitable dosage range or effective amount that provides any therapeuticeffect. As appreciated by one of ordinary skill in the art, atherapeutic effect depends on a number of factors. Dosages are generallyselected by the physician or other health care professional inaccordance with a variety of parameters known in the art, such asseverity of symptoms, history of the patient and the like. A dose may beabout 10⁴ cells to about 10⁶ cells, about 10⁶ cells to about 10⁸ cells,about 10⁸ to about 10¹¹ cells, or about 10⁸ to about 5×10¹⁰ cells. Adose may also about 10⁶ cells/m² to about 10¹⁰ cells/m², or about 10⁶cells/m² to about 10⁸ cells/m².

[0369] Proteins(s) of the invention, and/or nucleic acids encoding theprotein(s), can also be administered via liposomes, which may also serveto: 1) target the proteins(s) to a particular tissue, such as lymphoidtissue; 2) to target selectively to diseases cells; or, 3) to increasethe half-life of the peptide composition. Liposomes include emulsions,foams, micelles, insoluble monolayers, liquid crystals, phospholipiddispersions, lamellar layers and the like. In these preparations, thepeptide to be delivered is incorporated as part of a liposome, alone orin conjunction with a molecule which binds to a receptor prevalent amonglymphoid cells, such as monoclonal antibodies which bind to the CD45antigen, or with other therapeutic or immunogenic compositions. Thus,liposomes either filled or decorated with a desired peptide of theinvention can be directed to the site of lymphoid cells, where theliposomes then deliver the peptide compositions. Liposomes for use inaccordance with the invention are formed from standard vesicle-forminglipids, which generally include neutral and negatively chargedphospholipids and a sterol, such as cholesterol. The selection of lipidsis generally guided by consideration of, e.g., liposome size, acidlability and stability of the liposomes in the blood stream. A varietyof methods are available for preparing liposomes, as described in, e.g.,Szoka, et al., Ann. Rev. Biophys. Bioeng. 9:467 (1980), and U.S. Pat.Nos. 4,235,871, 4,501,728, 4,837,028, and 5,019,369.

[0370] For targeting cells of the immune system, a ligand to beincorporated into the liposome can include, e.g., antibodies orfragments thereof specific for cell surface determinants of the desiredimmune system cells. A liposome suspension containing a peptide may beadministered intravenously, locally, topically, etc. in a dose whichvaries according to, inter alia, the manner of administration, thepeptide being delivered, and the stage of the disease being treated.

[0371] For solid compositions, conventional nontoxic solid carriers maybe used which include, for example, pharmaceutical grades of mannitol,lactose, starch, magnesium stearate, sodium saccharin, talcum,cellulose, glucose, sucrose, magnesium carbonate, and the like. For oraladministration, a pharmaceutically acceptable nontoxic composition isformed by incorporating any of the normally employed excipients, such asthose carriers previously listed, and generally 10-95% of activeingredient, that is, one or more peptides of the invention, and morepreferably at a concentration of 25%-75%.

[0372] For aerosol administration, immunogenic peptides are preferablysupplied in finely divided form along with a surfactant and propellant.Typical percentages of peptides are about 0.01%-20% by weight,preferably about 1%-10%. The surfactant must, of course, be nontoxic,and preferably soluble in the propellant. Representative of such agentsare the esters or partial esters of fatty acids containing from about 6to 22 carbon atoms, such as caproic, octanoic, lauric, palmitic,stearic, linoleic, linolenic, olesteric and oleic acids with analiphatic polyhydric alcohol or its cyclic anhydride. Mixed esters, suchas mixed or natural glycerides may be employed. The surfactant mayconstitute about 0.1%-20% by weight of the composition, preferably about0.25-5%. The balance of the composition is ordinarily propellant. Acarrier can also be included, as desired, as with, e.g., lecithin forintranasal delivery.

[0373] XI.) Diagnostic and Prognostic Embodiments of 151P3D4.

[0374] As disclosed herein, 151P3D4 polynucleotides, polypeptides,reactive cytotoxic T cells (CTL), reactive helper T cells (HTL) andanti-polypeptide antibodies are used in well known diagnostic,prognostic and therapeutic assays that examine conditions associatedwith dysregulated cell growth such as cancer, in particular the cancerslisted in Table I (see, e.g., both its specific pattern of tissueexpression as well as its overexpression in certain cancers as describedfor example in the Example entitled “Expression analysis of 151P3D4 innormal tissues, and patient specimens”).

[0375] 151P3D4 can be analogized to a prostate associated antigen PSA,the archetypal marker that has been used by medical practitioners foryears to identify and monitor the presence of prostate cancer (see,e.g., Merrill et al., J. Urol. 163(2): 503-5120 (2000); Polascik et al.,J. Urol. August; 162(2):293-306 (1999) and Fortier et al., J. Nat.Cancer Inst. 91(19): 1635-1640(1999)). A variety of other diagnosticmarkers are also used in similar contexts including p53 and K-ras (see,e.g., Tulchinsky et al., Int J Mol Med Jul. 4, 1999 (1):99-102 andMinimoto et al., Cancer Detect Prev 2000;24(1):1-12). Therefore, thisdisclosure of 151P3D4 polynucleotides and polypeptides (as well as151P3D4 polynucleotide probes and anti-151P3D4 antibodies used toidentify the presence of these molecules) and their properties allowsskilled artisans to utilize these molecules in methods that areanalogous to those used, for example, in a variety of diagnostic assaysdirected to examining conditions associated with cancer.

[0376] Typical embodiments of diagnostic methods which utilize the151P3D4 polynucleotides, polypeptides, reactive T cells and antibodiesare analogous to those methods from well-established diagnostic assayswhich employ, e.g., PSA polynucleotides, polypeptides, reactive T cellsand antibodies. For example, just as PSA polynucleotides are used asprobes (for example in Northern analysis, see, e.g., Sharief et al.,Biochem. Mol. Biol. Int. 33(3):567-74(1994)) and primers (for example inPCR analysis, see, e.g., Okegawa et al., J. Urol. 163(4): 1189-1190(2000)) to observe the presence and/or the level of PSA mRNAs in methodsof monitoring PSA overexpression or the metastasis of prostate cancers,the 151P3D4 polynucleotides described herein can be utilized in the sameway to detect 151P3D4 overexpression or the metastasis of prostate andother cancers expressing this gene. Alternatively, just as PSApolypeptides are used to generate antibodies specific for PSA which canthen be used to observe the presence and/or the level of PSA proteins inmethods to monitor PSA protein overexpression (see, e.g., Stephan etal., Urology 55(4):560-3 (2000)) or the metastasis of prostate cells(see, e.g., Alanen et al., Pathol. Res. Pract. 192(3):233-7 (1996)), the151P3D4 polypeptides described herein can be utilized to generateantibodies for use in detecting 151P3D4 overexpression or the metastasisof prostate cells and cells of other cancers expressing this gene.

[0377] Specifically, because metastases involves the movement of cancercells from an organ of origin (such as the lung or prostate gland etc.)to a different area of the body (such as a lymph node), assays whichexamine a biological sample for the presence of cells expressing 151P3D4polynucleotides and/or polypeptides can be used to provide evidence ofmetastasis. For example, when a biological sample from tissue that doesnot normally contain 151P3D4-expressing cells (lymph node) is found tocontain 151P3D4-expressing cells such as the 151P3D4 expression seen inLAPC4 and LAPC9, xenografts isolated from lymph node and bonemetastasis, respectively, this finding is indicative of metastasis.

[0378] Alternatively 151P3D4 polynucleotides and/or polypeptides can beused to provide evidence of cancer, for example, when cells in abiological sample that do not normally express 151P3D4 or express151P3D4 at a different level are found to express 151P3D4 or have anincreased expression of 151P3D4 (see, e.g., the 151P3D4 expression inthe cancers listed in Table I and in patient samples etc. shown in theaccompanying Figures). In such assays, artisans may further wish togenerate supplementary evidence of metastasis by testing the biologicalsample for the presence of a second tissue restricted marker (inaddition to 151P3D4) such as PSA, PSCA etc. (see, e.g., Alanen et al.,Pathol. Res. Pract. 192(3): 233-237 (1999)).

[0379] Just as PSA polynucleotide fragments and polynucleotide variantsare employed by skilled artisans for use in methods of monitoring PSA,151P3D4 polynucleotide fragments and polynucleotide variants are used inan analogous manner. In particular, typical PSA polynucleotides used inmethods of monitoring PSA are probes or primers which consist offragments of the PSA cDNA sequence. Illustrating this, primers used toPCR amplify a PSA polynucleotide must include less than the whole PSAsequence to function in the polymerase chain reaction. In the context ofsuch PCR reactions, skilled artisans generally create a variety ofdifferent polynucleotide fragments that can be used as primers in orderto amplify different portions of a polynucleotide of interest or tooptimize amplification reactions (see, e.g., Caetano-Anolles, G.Biotechniques 25(3): 472-476, 478-480 (1998); Robertson et al., MethodsMol. Biol. 98:121-154 (1998)). An additional illustration of the use ofsuch fragments is provided in the Example entitled “Expression analysisof 151P3D4 in normal tissues, and patient specimens,” where a 151P3D4polynucleotide fragment is used as a probe to show the expression of151P3D4 RNAs in cancer cells. In addition, variant polynucleotidesequences are typically used as primers and probes for the correspondingmRNAs in PCR and Northern analyses (see, e.g., Sawai et al., FetalDiagn. Ther. Nov.-Dec. 11, 1996(6):407-13 and Current Protocols InMolecular Biology, Volume 2, Unit 2, Frederick M. Ausubel et al., eds.,1995)). Polynucleotide fragments and variants are useful in this contextwhere they are capable of binding to a target polynucleotide sequence(e.g., a 151P3D4 polynucleotide shown in FIG. 2 or variant thereof)under conditions of high stringency.

[0380] Furthermore, PSA polypeptides which contain an epitope that canbe recognized by an antibody or T cell that specifically binds to thatepitope are used in methods of monitoring PSA. 151P3D4 polypeptidefragments and polypeptide analogs or variants can also be used in ananalogous manner. This practice of using polypeptide fragments orpolypeptide variants to generate antibodies (such as anti-PSA antibodiesor T cells) is typical in the art with a wide variety of systems such asfusion proteins being used by practitioners (see, e.g., CurrentProtocols In Molecular Biology, Volume 2, Unit 16, Frederick M. Ausubelet al. eds., 1995). In this context, each epitope(s) functions toprovide the architecture with which an antibody or T cell is reactive.Typically, skilled artisans create a variety of different polypeptidefragments that can be used in order to generate immune responsesspecific for different portions of a polypeptide of interest (see, e.g.,U.S. Pat. No. 5,840,501 and U S. Pat. No. 5,939,533). For example it maybe preferable to utilize a polypeptide comprising one of the 151P3D4biological motifs discussed herein or a motif-bearing subsequence whichis readily identified by one of skill in the art based on motifsavailable in the art. Polypeptide fragments, variants or analogs aretypically useful in this context as long as they comprise an epitopecapable of generating an antibody or T cell specific for a targetpolypeptide sequence (e.g. a 151P3D4 polypeptide shown in FIG. 3).

[0381] As shown herein, the 151P3D4 polynucleotides and polypeptides (aswell as the 151P3D4 polynucleotide probes and anti-151P3D4 antibodies orT cells used to identify the presence of these molecules) exhibitspecific properties that make them useful in diagnosing cancers such asthose listed in Table I. Diagnostic assays that measure the presence of151P3D4 gene products, in order to evaluate the presence or onset of adisease condition described herein, such as prostate cancer, are used toidentify patients for preventive measures or further monitoring, as hasbeen done so successfully with PSA. Moreover, these materials satisfy aneed in the art for molecules having similar or complementarycharacteristics to PSA in situations where, for example, a definitediagnosis of metastasis of prostatic origin cannot be made on the basisof a test for PSA alone (see, e.g., Alanen et al., Pathol. Res. Pract.192(3): 233-237 (1996)), and consequently, materials such as 151P3D4polynucleotides and polypeptides (as well as the 151P3D4 polynucleotideprobes and anti-151P3D4 antibodies used to identify the presence ofthese molecules) need to be employed to confirm a metastases ofprostatic origin.

[0382] Finally, in addition to their use in diagnostic assays, the151P3D4 polynucleotides disclosed herein have a number of otherutilities such as their use in the identification of oncogeneticassociated chromosomal abnormalities in the chromosomal region to whichthe 151P3D4 gene maps (see the Example entitled “Chromosomal Mapping of151P3D4” below). Moreover, in addition to their use in diagnosticassays, the 151P3D4-related proteins and polynucleotides disclosedherein have other utilities such as their use in the forensic analysisof tissues of unknown origin (see, e.g., Takahama K Forensic Sci IntJun. 28, 1996; 80(1-2): 63-9).

[0383] Additionally, 151P3D4-related proteins or polynucleotides of theinvention can be used to treat a pathologic condition characterized bythe over-expression of 151P3D4. For example, the amino acid or nucleicacid sequence of FIG. 2 or FIG. 3, or fragments of either, can be usedto generate an immune response to a 151P3D4 antigen. Antibodies or othermolecules that react with 151P3D4 can be used to modulate the functionof this molecule, and thereby provide a therapeutic benefit.

[0384] XII.) Inhibition of 151P3D4 Protein Function

[0385] The invention includes various methods and compositions forinhibiting the binding of 151P3D4 to its binding partner or itsassociation with other protein(s) as well as methods for inhibiting151P3D4 function.

[0386] XII.A.) Inhibition of 151P3D4 with Intracellular Antibodies

[0387] In one approach, a recombinant vector that encodes single chainantibodies that specifically bind to 151P3D4 are introduced into 151P3D4expressing cells via gene transfer technologies. Accordingly, theencoded single chain anti-151P3D4 antibody is expressed intracellularly,binds to 151P3D4 protein, and thereby inhibits its function. Methods forengineering such intracellular single chain antibodies are well known.Such intracellular antibodies, also known as “intrabodies”, arespecifically targeted to a particular compartment within the cell,providing control over where the inhibitory activity of the treatment isfocused. This technology has been successfully applied in the art (forreview, see Richardson and Marasco, 1995, TIBTECH vol. 13). Intrabodieshave been shown to virtually eliminate the expression of otherwiseabundant cell surface receptors (see, e.g., Richardson et al., 1995,Proc. Natl. Acad. Sci. USA 92: 3137-3141; Beerli et al., 1994, J. Biol.Chem. 289: 23931-23936; Deshane et al., 1994, Gene Ther. 1: 332-337).

[0388] Single chain antibodies comprise the variable domains of theheavy and light chain joined by a flexible linker polypeptide, and areexpressed as a single polypeptide. Optionally, single chain antibodiesare expressed as a single chain variable region fragment joined to thelight chain constant region. Well-known intracellular traffickingsignals are engineered into recombinant polynucleotide vectors encodingsuch single chain antibodies in order to precisely target the intrabodyto the desired intracellular compartment. For example, intrabodiestargeted to the endoplasmic reticulum (ER) are engineered to incorporatea leader peptide and, optionally, a C-terminal ER retention signal, suchas the KDEL amino acid motif Intrabodies intended to exert activity inthe nucleus are engineered to include a nuclear localization signal.Lipid moieties are joined to intrabodies in order to tether theintrabody to the cytosolic side of the plasma membrane. Intrabodies canalso be targeted to exert function in the cytosol. For example,cytosolic intrabodies are used to sequester factors within the cytosol,thereby preventing them from being transported to their natural cellulardestination.

[0389] In one embodiment, intrabodies are used to capture 151P3D4 in thenucleus, thereby preventing its activity within the nucleus. Nucleartargeting signals are engineered into such 151P3D4 intrabodies in orderto achieve the desired targeting. Such 151P3D4 intrabodies are designedto bind specifically to a particular 151P3D4 domain. In anotherembodiment, cytosolic intrabodies that specifically bind to a 151P3D4protein are used to prevent 151P3D4 from gaining access to the nucleus,thereby preventing it from exerting any biological activity within thenucleus (e.g., preventing 151P3D4 from forming transcription complexeswith other factors).

[0390] In order to specifically direct the expression of suchintrabodies to particular cells, the transcription of the intrabody isplaced under the regulatory control of an appropriate tumor-specificpromoter and/or enhancer. In order to target intrabody expressionspecifically to prostate, for example, the PSA promoter and/orpromoter/enhancer can be utilized (See, for example, U.S. Pat. No.5,919,652 issued Jul. 6, 1999).

[0391] XII.B.) Inhibition of 151P3D4 with Recombinant Proteins

[0392] In another approach, recombinant molecules bind to 151P3D4 andthereby inhibit 151P3D4 function. For example, these recombinantmolecules prevent or inhibit 151P3D4 from accessing/binding to itsbinding partner(s) or associating with other protein(s). Suchrecombinant molecules can, for example, contain the reactive part(s) ofa 151P3D4 specific antibody molecule. In a particular embodiment, the151P3D4 binding domain of a 151P3D4 binding partner is engineered into adimeric fusion protein, whereby the fusion protein comprises two 151P3D4ligand binding domains linked to the Fc portion of a human IgG, such ashuman IgG1. Such IgG portion can contain, for example, the C_(H)2 andC_(H)3 domains and the hinge region, but not the C_(H)1 domain. Suchdirneric fusion proteins are administered in soluble form to patientssuffering from a cancer associated with the expression of 151P3D4,whereby the dimeric fusion protein specifically binds to 151P3D4 andblocks 151P3D4 interaction with a binding partner. Such dimeric fusionproteins are further combined into multimeric proteins using knownantibody linking technologies.

[0393] XII.C.) Inhibition of 151P3D4 Transcription or Translation

[0394] The present invention also comprises various methods andcompositions for inhibiting the transcription of the 151P3D4 gene.Similarly, the invention also provides methods and compositions forinhibiting the translation of 151P3D4 mRNA into protein.

[0395] In one approach, a method of inhibiting the transcription of the151P3D4 gene comprises contacting the 151P3D4 gene with a 151P3D4antisense polynucleotide. In another approach, a method of inhibiting151P3D4 mRNA translation comprises contacting a 151P3D4 mRNA with anantisense polynucleotide. In another approach, a 151P3D4 specificribozyme is used to cleave a 151P3D4 message, thereby inhibitingtranslation. Such antisense and ribozyme based methods can also bedirected to the regulatory regions of the 15P3D4 gene, such as 151P3D4promoter and/or enhancer elements. Similarly, proteins capable ofinhibiting a 151P3D4 gene transcription factor are used to inhibit151P3D4 mRNA transcription. The various polynucleotides and compositionsuseful in the aforementioned methods have been described above. The useof antisense and ribozyme molecules to inhibit transcription andtranslation is well known in the art.

[0396] Other factors that inhibit the transcription of 151P3D4 byinterfering with 151P3D4 transcriptional activation are also useful totreat cancers expressing 151P3D4. Similarly, factors that interfere with151P3D4 processing are useful to treat cancers that express 151P3D4.Cancer treatment methods utilizing such factors are also within thescope of the invention.

[0397] XII.D.) General Considerations for Therapeutic Strategies

[0398] Gene transfer and gene therapy technologies can be used todeliver therapeutic polynucleotide molecules to tumor cells synthesizing151P3D4 (i.e., antisense, ribozyme, polynucleotides encoding intrabodiesand other 151P3D4 inhibitory molecules). A number of gene therapyapproaches are known in the art. Recombinant vectors encoding 151P3D4antisense polynucleotides, ribozymes, factors capable of interferingwith 151P3D4 transcription, and so forth, can be delivered to targettumor cells using such gene therapy approaches.

[0399] The above therapeutic approaches can be combined with any one ofa wide variety of surgical, chemotherapy or radiation therapy regimens.The therapeutic approaches of the invention can enable the use ofreduced dosages of chemotherapy (or other therapies) and/or lessfrequent administration, an advantage for all patients and particularlyfor those that do not tolerate the toxicity of the chemotherapeuticagent well.

[0400] The anti-tumor activity of a particular composition (e.g.,antisense, ribozyme, intrabody), or a combination of such compositions,can be evaluated using various in vitro and in vivo assay systems. Invitro assays that evaluate therapeutic activity include cell growthassays, soft agar assays and other assays indicative of tumor promotingactivity, binding assays capable of determining the extent to which atherapeutic composition will inhibit the binding of 151P3D4 to a bindingpartner, etc.

[0401] In vivo, the effect of a 151P3D4 therapeutic composition can beevaluated in a suitable animal model. For example, xenogenic prostatecancer models can be used, wherein human prostate cancer explants orpassaged xenograft tissues are introduced into immune compromisedanimals, such as nude or SCID mice (Klein et al., 1997, Nature Medicine3: 402-408). For example, PCT Patent Application WO98/16628 and U.S.Pat. No. 6,107,540 describe various xenograft models of human prostatecancer capable of recapitulating the development of primary tumors,micrometastasis, and the formation of osteoblastic metastasescharacteristic of late stage disease. Efficacy can be predicted usingassays that measure inhibition of tumor formation, tumor regression ormetastasis, and the like.

[0402] In vivo assays that evaluate the promotion of apoptosis areuseful in evaluating therapeutic compositions. In one embodiment,xenografts from tumor bearing mice treated with the therapeuticcomposition can be examined for the presence of apoptotic foci andcompared to untreated control xenograft-bearing mice. The extent towhich apoptotic foci are found in the tumors of the treated miceprovides an indication of the therapeutic efficacy of the composition.

[0403] The therapeutic compositions used in the practice of theforegoing methods can be formulated into pharmaceutical compositionscomprising a carrier suitable for the desired delivery method. Suitablecarriers include any material that when combined with the therapeuticcomposition retains the anti-tumor function of the therapeuticcomposition and is generally non-reactive with the patient's immunesystem. Examples include, but are not limited to, any of a number ofstandard pharmaceutical carriers such as sterile phosphate bufferedsaline solutions, bacteriostatic water, and the like (see, generally,Remington's Pharmaceutical Sciences 16^(th) Edition, A. Osal., Ed.,1980).

[0404] Therapeutic formulations can be solubilized and administered viaany route capable of delivering the therapeutic composition to the tumorsite. Potentially effective routes of administration include, but arenot limited to, intravenous, parenteral, intraperitoneal, intramuscular,intratumor, intradermal, intraorgan, orthotopic, and the like. Apreferred formulation for intravenous injection comprises thetherapeutic composition in a solution of preserved bacteriostatic water,sterile unpreserved water, and/or diluted in polyvinylchloride orpolyethylene bags containing 0.9% sterile Sodium Chloride for Injection,USP. Therapeutic protein preparations can be lyophilized and stored assterile powders, preferably under vacuum, and then reconstituted inbacteriostatic water (containing for example, benzyl alcoholpreservative) or in sterile water prior to injection.

[0405] Dosages and administration protocols for the treatment of cancersusing the foregoing methods will vary with the method and the targetcancer, and will generally depend on a number of other factorsappreciated in the art.

[0406] XIII.) Kits

[0407] For use in the diagnostic and therapeutic applications describedherein, kits are also within the scope of the invention. Such kits cancomprise a carrier, package or container that is compartmentalized toreceive one or more containers such as vials, tubes, and the like, eachof the container(s) comprising one of the separate elements to be usedin the method. For example, the container(s) can comprise a probe thatis or can be detectably labeled. Such probe can be an antibody orpolynucleotide specific for a 151P3D4-related protein or a 151P3D4 geneor message, respectively. Where the method utilizes nucleic acidhybridization to detect the target nucleic acid, the kit can also havecontainers containing nucleotide(s) for amplification of the targetnucleic acid sequence and/or a container comprising a reporter-means,such as a biotin-binding protein, such as avidin or streptavidin, boundto a reporter molecule, such as an enzymatic, florescent, orradioisotope label. The kit can include all or part of the amino acidsequence of FIG. 2 or FIG. 3 or analogs thereof, or a nucleic acidmolecules that encodes such amino acid sequences.

[0408] The kit of the invention will typically comprise the containerdescribed above and one or more other containers comprising materialsdesirable from a commercial and user standpoint, including buffers,diluents, filters, needles, syringes, and package inserts withinstructions for use.

[0409] A label can be present on the container to indicate that thecomposition is used for a specific therapy or non-therapeuticapplication, and can also indicate directions for either in vivo or invitro use, such as those described above. Directions and or otherinformation can also be included on an insert which is included with thekit.

EXAMPLES

[0410] Various aspects of the invention are further described andillustrated by way of the several examples that follow, none of whichare intended to limit the scope of the invention.

Example 1

[0411] SSH-Generated Isolation of a cDNA Fragment of the 151P3D4 Gene

[0412] To isolate genes that are over-expressed in bladder cancer weused the Suppression Subtractive Hybridization (SSH) procedure usingcDNA derived from the LNCaP prostate cancer cell line.

[0413] The 151P3D4 SSH cDNA sequence was derived from a subtractionconsisting of two different populations of LNCaP cells. The 151P3D4 SSHcDNA sequence of417 bp is listed in FIG. 1.

[0414] The full-length 151P3D4 v.1 clone 1-placenta was cloned fromnormal placenta cDNA, revealing an ORF of 354 amino acids (FIG. 2 andFIG. 3). Other variants of 151P3D4 were also identified and these arelisted in FIGS. 2 and 3.

[0415] Materials and Methods

[0416] Human Tissues:

[0417] The patient cancer and normal tissues were purchased fromdifferent sources such as the NDRI (Philadelphia, Pa.). mRNA for somenormal tissues were purchased from Clontech, Palo Alto, Calif.

[0418] RNA Isolation:

[0419] Tissues were homogenized in Trizol reagent (Life Technologies,Gibco BRL) using 10 ml/g tissue isolate total RNA. Poly A RNA waspurified from total RNA using Qiagen's Oligotex mRNA Mini and Midi kits.Total and mRNA were quantified by spectrophotometric analysis (O.D.260/280 nm) and analyzed by gel electrophoresis.

[0420] Oligonucleotides:

[0421] The following HPLC purified oligonucleotides were used. DPNCDN(cDNA synthesis primer): (SEQ ID NO:_(——)) 5′TTTTGATCAAGCTT₃₀3′ Adaptor1: (SEQ ID NO:_(——)) 5′CTAATACGACTCACTATAGGGCTCGAGCGGCCGCCCGGGCAG3′ (SEQID NO:_(——)) 3′GGCCCGTCCTAG5′ Adaptor 2: (SEQ ID NO:_(——))5′GTAATACGACTCACTATAGGGCAGCGTGGTCGCGGCCGAG3′ (SEQ ID NO:_(——))3′CGGCTCCTAG5′ PCR primer 1: (SEQ ID NO:_(——))5′CTAATACGACTCACTATAGGGC3′ Nested primer (NP)1: (SEQ ID NO:_(——))5′TCGAGCGGCCGCCCGGGCAGGA3′ Nested primer (NP)2: (SEQ ID NO:_(——))5′AGCGTGGTCGCGGCCGAGGA3′

[0422] Suppression Subtractive Hybridization:

[0423] Suppression Subtractive Hybridization (SSH) was used to identifycDNAs corresponding to genes that may be differentially expressed inprostate cancer. The SSH reaction utilized cDNA from two differentclones of LNCaP cells.

[0424] The gene 151P3D4 was derived from one population of LNCaP cellsminus another population of LNCaP cells cDNA subtraction. The 151P3D4SSH DNA sequence (FIG. 1) was identified.

[0425] The cDNA derived from one population of LNCaP cells was used asthe source of the “driver” cDNA, while the cDNA from another populationof LNCaP cells was used as the source of the “tester” cDNA. Doublestranded cDNAs corresponding to tester and driver cDNAs were synthesizedfrom 2 μg of poly(A)⁺ RNA isolated from the relevant tissue, asdescribed above, using CLONTECH's PCR-Select cDNA Subtraction Kit and 1ng of oligonucleotide DPNCDN as primer. First- and second-strandsynthesis were carried out as described in the Kit's user manualprotocol (CLONTECH Protocol No. PT1117-1, Catalog No. K1804-1). Theresulting cDNA was digested with Dpn II for 3 hrs at 37° C. DigestedcDNA was extracted with phenolchloroform (1:1) and ethanol precipitated.

[0426] Driver cDNA was generated by combining in a 1:1 ratio Dpn IIdigested cDNA from the relevant source (see above). Tester cDNA wasgenerated by diluting 1 μl of Dpn II digested cDNA from the relevantsource (see above) (400 ng) in 5 μl of water. The diluted cDNA (2 μl,160 ng) was then ligated to 2 μl of Adaptor 1 and Adaptor 2 (10 μM), inseparate ligation reactions, in a total volume of 10 μl at 16° C.overnight, using 400 u of T4 DNA ligase (CLONTECH). Ligation wasterminated with 1 μl of 0.2 M EDTA and heating at 72° C. for 5 min.

[0427] The first hybridization was performed by adding 1.5 μl (600 ng)of driver cDNA to each of two tubes containing 1.5 μl (20 ng) Adaptor 1-and Adaptor 2-ligated tester cDNA. In a final volume of 4 μl, thesamples were overlaid with mineral oil, denatured in an MJ Researchthermal cycler at 98° C. for 1.5 minutes, and then were allowed tohybridize for 8 hrs at 68° C. The two hybridizations were then mixedtogether with an additional 1 μl of fresh denatured driver cDNA and wereallowed to hybridize overnight at 68° C. The second hybridization wasthen diluted in 200 μl of 20 mM Hepes, pH 8.3, 50 mM NaCl, 0.2 mM EDTA,heated at 70° C. for 7 min. and stored at −20° C.

[0428] PCR Amplification Cloning and Sequencing of Gene FragmentsGenerated from SSH:

[0429] To amplify gene fragments resulting from SSH reactions, two PCRamplifications were performed. In the primary PCR reaction 1 μl of thediluted final hybridization mix was added to 1 μl of PCR primer 1 (10μM), 0.5 μl dNTP mix (10 μM), 2.5 μl 10× reaction buffer (CLONTECH) and0.5 μl 50× Advantage cDNA polymerase Mix (CLONTECH) in a final volume of25 μl. PCR 1 was conducted using the following conditions: 75° C. for 5min., 94° C. for 25 sec., then 27 cycles of 94° C. for 10 sec, 66° C.for 30 sec, 72° C. for 1.5 min. Five separate primary PCR reactions wereperformed for each experiment. The products were pooled and diluted 1:10with water. For the secondary PCR reaction, 1 μl from the pooled anddiluted primary PCR reaction was added to the same reaction mix as usedfor PCR 1, except that primers NP1 and NP2 (10 μM) were used instead ofPCR primer 1. PCR 2 was performed using 10-12 cycles of 94° C. for 10sec, 68° C. for 30 sec, and 72° C. for 1.5 minutes. The PCR productswere analyzed using 2% agarose gel electrophoresis.

[0430] The PCR products were inserted into pCR2.1 using the T/A vectorcloning kit (Invitrogen). Transformed E. coli were subjected toblue/white and ampicillin selection. White colonies were picked andarrayed into 96 well plates and were grown in liquid culture overnight.To identify inserts, PCR amplification was performed on 1 ml ofbacterial culture using the conditions of PCR1 and NP1 and NP2 asprimers. PCR products were analyzed using 2% agarose gelelectrophoresis.

[0431] Bacterial clones were stored in 20% glycerol in a 96 well format.Plasmid DNA was prepared, sequenced, and subjected to nucleic acidhomology searches of the GenBank, dBest, and NCI-CGAP databases.

[0432] RT-PCR Expression Analysis:

[0433] First strand cDNAs can be generated from 1 μg of mRNA with oligo(dT)12-18 priming using the Gibco-BRL Superscript Preamplificationsystem. The manufacturer's protocol was used which included anincubation for 50 min at 42° C. with reverse transcriptase followed byRNAse H treatment at 37° C. for 20 min. After completing the reaction,the volume can be increased to 200 μl with water prior to normalization.First strand cDNAs from 16 different normal human tissues can beobtained from Clontech.

[0434] Normalization of the first strand cDNAs from multiple tissues wasperformed by using the primers 5′atatcgccgcgctcgtcgtcgacaa3′ (SEQ ID NO:______) and 5′agccacacgcagctcattgtagaagg 3′ (SEQ ID NO: _____) toamplify β-actin. First strand cDNA (5 μl) were amplified in a totalvolume of 50 μl containing 0.4 μM primers, 0.2 μM each dNTPs, 1XPCRbuffer (Clontech, 10 mM Tris-HCL, 1.5 mM MgCl₂, 50 mM KCl, pH8.3) and 1XKlentaq DNA polymerse (Clontech). Five μl of the PCR reaction can beremoved at 18, 20, and 22 cycles and used for agarose gelelectrophoresis. PCR was performed using an MJ Research thermal cyclerunder the following conditions: initial denaturation can be at 94° C.for 15 sec, followed by a 18, 20, and 22 cycles of 94° C. for 15, 65° C.for 2 min, 72° C. for 5 sec. A final extension at 72° C. was carried outfor 2 min. After agarose gel electrophoresis, the band intensities ofthe 283 b.p. β-actin bands from multiple tissues were compared by visualinspection. Dilution factors for the first strand cDNAs were calculatedto result in equal β-actin band intensities in all tissues after 22cycles of PCR. Three rounds of normalization can be required to achieveequal band intensities in all tissues after 22 cycles of PCR.

[0435] To determine expression levels of the 151P3D4 gene, 5 μl ofnormalized first strand cDNA were analyzed by PCR using 26, and 30cycles of amplification. Semi-quantitative expression analysis can beachieved by comparing the PCR products at cycle numbers that give lightband intensities. The primers used for RT-PCR were designed using the151P3D4 SSH sequence and are listed below: 151P3D4.15′-CCCACCAAACTGACCTATGATGAA-3′ (SEQ ID NO: ) 151P3D4.25′-TGTATGCTCTGAAGCAGTAGACACC-3′ (SEQ ID NO: )

[0436] A typical RT-PCR expression study is shown in FIG. 14. Firststrand cDNA was prepared from vital pool 1 (liver, lung and kidney),vital pool 2 (pancreas, colon and stomach), bladder cancer pool, kidneycancer pool, colon cancer pool, lung cancer pool, ovary cancer pool,breast cancer pool, and cancer metastasis pool. Normalization wasperformed by PCR using primers to actin and GAPDH. Semi-quantitativePCR, using primers to 151P3D4, was performed at 26 and 30 cycles ofamplification. Results show strong expression of 151P3D4 in ovary cancerpool. Expression of 151P3D4 was also detected in bladder cancer pool,kidney cancer pool, colon cancer pool, lung cancer pool, breast cancerpool, cancer metastasis pool, vital pool 2, but not in vital pool 1.

[0437] Example 2

[0438] Full Length Cloning of 151P3D4

[0439] To isolate genes that are expressed in prostate cancer, we usedthe Suppression Subtractive Hybridization (SSH) procedure using cDNAderived from two different populations of LNCaP cells.

[0440] The 151P3D4 SSH cDNA sequence was derived from a subtractionconsisting of one population of LNCaP cells minus another population ofLNCaP cells. The 151P3D4 SSH cDNA sequence of417 bp is listed in FIG. 1.

[0441] The full-length 151P3D4 v.1 (151P3D4 clone 1-placenta) was clonedfrom normal placenta cDNA, revealing an ORF of 354 amino acids (FIG. 2and FIG. 3). 151P3D4 v.1 showed 99% identity over 1492 nucleotides withthe human mRNA for cartilage link protein (gi463246) (FIG. 4A). 151P3D4v.1 protein showed 100% identity over 354 amino acids with the humancartilage link protein (FIG. 4B). Also, 151P3D4 v.1 was 96% identicalover 355 amino acids with the mouse link protein (gi4218976) (FIG. 4C)

[0442] Other variants of 151P3D4 were also identified and these arelisted in FIGS. 2 and 3. 151P3D4 v.2 codes for a novel protein thatcontains sequences not present in 151P3D4 v.1. These are from aminoacids 1 to 400. Amino acids 401 to 721 of 151P3D4 v.2 align with 151P3D4v.1 at positions 34 to 354 (FIG. 4D). A small portion of 151P3D4 v.2demonstrates homology to the hypothetical protein XP_(—)094318 (FIG.4E). The two proteins show 99% identity over 168 amino acids. The othervariants 151P3D4 v.3 through v.11 each differ from 151P3D4 v.1 by onenucleotide (FIG. 10).

[0443] Example 3

[0444] Chromosomal Mapping of 151P3D4

[0445] Chromosomal localization can implicate genes in diseasepathogenesis. Several chromosome mapping approaches are availableincluding fluorescent in situ hybridization (FISH), human/hamsterradiation hybrid (RH) panels (Walter et al., 1994; Nature Genetics 7:22;Research Genetics, Huntsville Ala.), human-rodent somatic cell hybridpanels such as is available from the Coriell Institute (Camden, N.J.),and genomic viewers utilizing BLAST homologies to sequenced and mappedgenomic clones (NCBI, Bethesda, Md.).

[0446] 151P3D4 maps to chromosome 5q13-q14.1 using 151P3D4 sequence andthe NCBI BLAST tool:(http://www.ncbi.nlm.nih.gov/genome/seq/page.cgi?F=HsBlast.html&&ORG=Hs).

Example 4

[0447] Expression Analysis of 151P3D4 in Normal Tissues and PatientSpecimens

[0448] Expression analysis by RT-PCR demonstrated that 151P3D4 isstrongly expressed in cancer patient specimens (FIG. 14). First strandcDNA was prepared from vital pool 1 (liver, lung and kidney), vital pool2 (pancreas, colon and stomach), bladder cancer pool, kidney cancerpool, colon cancer pool, lung cancer pool, ovary cancer pool, breastcancer pool, and cancer metastasis pool. Normalization was performed byPCR using primers to actin and GAPDH. Semi-quantitative PCR, usingprimers to 151P3D4, was performed at 26 and 30 cycles of amplification.Results show strong expression of 151P3D4 in ovary cancer pool.Expression of 151P3D4 was also detected in bladder cancer pool, kidneycancer pool, colon cancer pool, lung cancer pool, breast cancer pool,cancer metastasis pool, vital pool 2, but not in vital pool 1.

[0449] Extensive northern blot analysis of 151P3D4 in multiple humannormal tissues is shown in FIG. 15. Two multiple tissue northern blots(Clontech) both with 2 μg of mRNA/lane were probed with the 151P3D4 SSHsequence. Size standards in kilobases (kb) are indicated on the side.Results show expression of 151P3D4 in small intestine and placenta.Lower level expression was also detected in heart and colon, but not inthe other normal tissues tested.

[0450] Expression of 151P3D4 in patient bladder cancer specimens isshown in FIG. 16. RNA was extracted from normal bladder (NB), bladdercancer cell lines (CL; UM-UC-3, J82, SCaBER), bladder cancer patienttumors (T) and normal adjacent tissue (NAT). Northern blots with 10 μgof total RNA were probed with the 151P3D4 SSH sequence. Size standardsin kilobases are indicated on the side. Results show expression of151P3D4 in patient bladder cancer tissues, and in UM-UC-3 bladder cancercell lines, but not in normal bladder nor in the other bladder cancercell lines tested.

[0451]FIG. 17 shows that 151P3D4 was expressed in kidney cancer patientspecimens. RNA was extracted from kidney cancer cell lines (CL: 769-P,A498, SW839), normal kidney (NK), kidney cancer patient tumors (T) andtheir normal adjacent tissues (NAT). Northern blots with 10 μg of totalRNA were probed with the 151P3D4 SSH sequence. Size standards inkilobases are on the side. Results show expression of 151P3D4 in patientkidney tumor tissues, but not in normal kidney, nor in the cell linestested.

[0452] Expression of 151P3D4 was also detected in ovary cancer patientspecimen (FIG. 18). RNA was extracted from ovary and cervical cancercell lines (CL), normal ovary (N), and ovary cancer patient tumor (T).Northern blots with 10 μg of total RNA were probed with the 151P3D4 SSHsequence. Size standards in kilobases are on the side. Results showstrong expression of 151P3D4 in patient ovary cancer tissues, but not innormal ovary nor in the ovary and cervical cancer cell lines.

[0453]FIG. 19 shows that 151P3D4 was also expressed in stomach cancersand in uterus cancers. Expression of 151P3D4 was assayed in a panel ofhuman stomach and uterus cancers (T) and their respective matched normaltissues (N) on RNA dot blots. 151P3D4 expression was seen in bothstomach and uterus cancers.

[0454] The restricted expression of 151P3D4 in normal tissues and theexpression detected in human cancers suggest that 151P3D4 is a potentialtherapeutic target and a diagnostic marker for human cancers.

Example 5

[0455] Transcript Variants of 151P3D4

[0456] Transcript variants are variants of matured mRNA from the samegene by alternative transcription or alternative splicing. Alternativetranscripts are transcripts from the same gene but start transcriptionat different points. Splice variants are mRNA variants spliceddifferently from the same transcript. In eukaryotes, when a multi-exongene is transcribed from genomic DNA, the initial RNA is spliced toproduce functional mRNA, which has only exons and is used fortranslation into an amino acid sequence. Accordingly, a given gene canhave zero to many alternative transcripts and each transcript can havezero to many splice variants. Each transcript variant has a unique exonmakeup, and can have different coding and/or non-coding (5′ or 3′ end)portions, from the original transcript. Transcript variants can code forsimilar or different proteins with the same or a similar function or mayencode proteins with different functions, and may be expressed in thesame tissue at the same time, or at different tissue, or at differenttimes, proteins encoded by transcript variants can have similar ordifferent cellular or extracellular localizations, i.e., be secreted.

[0457] Transcript variants are identified by a variety of art-acceptedmethods. For example, alternative transcripts and splice variants areidentified in a full-length cloning experiment, or by use of full-lengthtranscript and EST sequences. First, all human ESTs were grouped intoclusters which show direct or indirect identity with each other. Second,ESTs in the same cluster were further grouped into sub-clusters andassembled into a consensus sequence. The original gene sequence iscompared to the consensus sequence(s) or other full-length sequences.Each consensus sequence is a potential splice variant for that gene(see, e.g.,http://www.doubletwist.com/products/c11_agentsOverview.jhtml). Even whena variant is identified that is not a full-length clone, that portion ofthe variant is very useful for antigen generation and for furthercloning of the full-length splice variant, using techniques known in theart.

[0458] Moreover, computer programs are available in the art thatidentify transcript variants based on genomic sequences. Genomic-basedtranscript variant identification programs include FgenesH (A. Salamovand V. Solovyev, “Ab initio gene finding in Drosophila genomic DNA,”Genome Research. April 2000; 10(4):516-22); Grail(http://compbio.ornl.gov/Grail-bin/EmptyGrailForm) and GenScan(http://genes.mit.edu/GENSCAN.html). For a general discussion of splicevariant identification protocols see., e.g., Southan, C., A genomicperspective on human proteases, FEBS Lett. Jun. 8, 2001; 498(2-3):214-8;de Souza, S. J., et al., Identification of human chromosome 22transcribed sequences with ORF expressed sequence tags, Proc. Natl AcadSci USA. Nov. 7, 2000; 97(23): 12690-3.

[0459] To further confirm the parameters of a transcript variant, avariety of techniques are available in the art, such as full-lengthcloning, proteomic validation, PCR-based validation, and 5′ RACEvalidation, etc. (see e.g., Proteomic Validation: Brennan, S. O., etal., Albumin banks peninsula: a new termination variant characterized byelectrospray mass spectrometry, Biochem Biophys Acta. Aug. 17, 1999;1433(1-2):321-6; Ferranti P, et al., Differential splicing ofpre-messenger RNA produces multiple forms of mature caprinealpha(s1)-casein, Eur J Biochem. Oct. 1, 1997; 249(1): 1-7. ForPCR-based Validation: Wellmann S, et al., Specific reversetranscription-PCR quantification of vascular endothelial growth factor(VEGF) splice variants by LightCycler technology, Clin Chem. April 2001;47(4):654-60; Jia, H. P., et al., Discovery of new human beta-defensinsusing a genomics-based approach, Gene. Jan. 24, 2001; 263(1-2):211-8.For PCR-based and 5′ RACE Validation: Brigle, K. E., et al.,Organization of the murine reduced folate carrier gene andidentification of variant splice forms, Biochem Biophys Acta. Aug. 7,1997; 1353(2): 191-8).

[0460] It is known in the art that genomic regions are modulated incancers. When the genomic region to which a gene maps is modulated in aparticular cancer, the alternative transcripts or splice variants of thegene are modulated as well. Disclosed herein is that 151P3D4 has aparticular expression profile. Alternative transcripts and splicevariants of 151P3D4 that are structurally and/or functionally similar to151P3D4 share this expression pattern, thus serving as tumor associatedmarkers/antigens.

[0461] The exon composition of the original transcript, designated as151P3D4 v.1, is shown in Table LII (A). Using the full-length gene andEST sequences, one alternative transcript was identified, designated as151P3D4 v.2. Compared with 151P3D4 v.1, transcript variant 151P3D4 v.2has 10 exons, as shown in Table LII (B) and FIG. 12. Exons 8 and 9 arethe same as exons 3 and 4 of 151P3D4 v.1, and exon 10 is the codingportion of exon 5 of 151P3D4 v.1. Each different combination of exons inspatial order, e.g. exons 2 and 3, is a potential splice variant. FIG.12 shows the schematic alignment of exons of the two transcriptvariants.

[0462] Table LIII shows nucleotide sequence of the transcript variant,151P3D4 v.2 (see also FIG. 2B). Table LIV shows the alignment of thetranscript variant 151P3D4 v.2 with nucleic acid sequence of 151P3D4v.1. FIG. 3B provides the amino acid translation of the transcriptvariant 151P3D4 v.2 for the identified reading frame orientation. TableLV displays alignments of the amino acid sequence encoded by thetranscript variant 151P3D4 v.2 with that of 151P3D4 v.1.

Example 6

[0463] Single Nucleotide Polymorphisms of 151P3D4

[0464] Single Nucleotide Polymorphism (SNP) is a single base pairvariation in nucleotide sequences. At a specific point of the genome,there are four possible nucleotide base pairs: A/T, C/G, G/C and T/A.Genotype refers to the base pair make-up of one or more spots in thegenome of an individual, while haplotype refers to base pair make-up ofmore than one varied spots on the same DNA molecule (chromosome inhigher organism). SNPs that occur on a cDNA are called cSNPs. ThesecSNPs may change amino acids of the protein encoded by the gene and thuschange the functions of the protein. Some SNPs cause inherited diseasesand some others contribute to quantitative variations in phenotype andreactions to environmental factors including diet and drugs amongindividuals. Therefore, SNPs and/or combinations of alleles (calledhaplotypes) have many applications including diagnosis of inheriteddiseases, determination of drug reactions and dosage, identification ofgenes responsible for disearses and discovery of genetic relationshipbetween individuals (P. Nowotny, J. M. Kwon and A. M. Goate, “SNPanalysis to dissect human traits,” Curr. Opin. Neurobiol. October 2001;11(5):637-641; M. Pirmohamed and B. K. Park, “Genetic susceptibility toadverse drug reactions,” Trends Pharmacol. Sci. June 2001;22(6):298-305; J. H. Riley, C. J. Allan, E. Lai and A. Roses, “The useof single nucleotide polymorphisms in the isolation of common diseasegenes,” Pharmacogenomics. February 2000; 1(1):39-47; R. Judson, J. C.Stephens and A. Windemuth, “The predictive power of haplotypes inclinical response,” Pharmacogenomics. February 2000; 1(1):15-26).

[0465] SNPs are identified by a variety of art-accepted methods (P.Bean, “The promising voyage of SNP target discovery,” Am. Clin. Lab.October-November; 2001; 20(9): 18-20; K. M. Weiss, “In search of humanvariation,” Genome Res. July 1998; 8(7):691-697; M. M. She, “Enablinglarge-scale pharmacogenetic studies by high-throughput mutationdetection and genotyping technologies,” Clin. Chem. February 2001;47(2): 164-172). For example, SNPs are identified by sequencing DNAfragments that show polymorphism by gel-based methods such asrestriction fragment length polymorphism (RFLP) and denaturing gradientgel electrophoresis (DGGE). They can also be discovered by directsequencing of DNA samples pooled from different individuals or bycomparing sequences from different DNA samples. With the rapidaccumulation of sequence data in public and private databases, one candiscover SNPs by comparing sequences using computer programs (Z. Gu, L.Hillier and P. Y. Kwok, “Single nucleotide polymorphism hunting incyberspace,” Hum. Mutat. 1998; 12(4):221-225). SNPs can be verified andgenotype or haplotype of an individual can be determined by a variety ofmethods including direct sequencing and high throughput microarrays (P.Y. Kwok, “Methods for genotyping single nucleotide polymorphisms,” Annu.Rev. Genomics Hum. Genet. 2001; 2:235-258; M. Kokoris, K. Dix, K.Moynihan, J. Mathis, B. Erwin, P. Grass, B. Hines and A. Duesterhoeft,“High-throughput SNP genotyping with the Masscode system,” Mol. Diagn.December 2000; 5(4):329-340).

[0466] Using the methods described above, nine SNPs were identified inthe original transcript, 151P3D4 v.1, at positions 154 (A/G), 218 (C/G),219 (G/C), 999 (C/G), 1326 (C/T), 1399 (T/C), 1400 (C/T), 1653 (T/C) and1726 (A/G). The transcripts or proteins with alternative alleles weredesignated as variants 151P3D4 v.3, v.4, v.5, v.6, v.7, v.8, v.9, v.10and v.11. FIGS. 10 and 12 show the schematic alignment of the nucleotidevariants. FIG. 11 shows the schematic alignment of protein variants,corresponding to nucleotide variants. Nucleotide variants that code forthe same amino acid sequence as variant 1 are not shown in FIG. 11.These alleles of the SNPs, though shown separately here, can occur indifferent combinations (haplotypes) and in any one of the transcriptvariants that contains the sequence context of the SNPs, e.g., 151P3D4v.7.

Example 7

[0467] Production of Recombinant 151P3D4 in Prokaryotic Systems

[0468] To express recombinant 151P3D4 and 151P3D4 variants inprokaryotic cells, the full or partial length 151P3D4 and 151P3D4variant cDNA sequences are cloned into any one of a variety ofexpression vectors known in the art. One or more of the followingregions of 151P3D4 variants are expressed: the full length sequencepresented in FIGS. 2 and 3, or any 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or more contiguousamino acids from 151P3D4, variants, or analogs thereof.

[0469] A. In vitro Transcription and Translation Constructs:

[0470] pCRII: To generate 151P3D4 sense and anti-sense RNA probes forRNA in situ investigations, pCRII constructs (Invitrogen, CarlsbadCalif.) are generated encoding either all or fragments of the 151P3D4cDNA. The pCRII vector has Sp6 and T7 promoters flanking the insert todrive the transcription of 151P3D4 RNA for use as probes in RNA in situhybridization experiments. These probes are used to analyze the cell andtissue expression of 151P3D4 at the RNA level. Transcribed 151P3D4 RNArepresenting the cDNA amino acid coding region of the 151P3D4 gene isused in in vitro translation systems such as the TnT™ CoupledReticulolysate System (Promega, Corp., Madison, Wis.) to synthesize151P3D4 protein.

[0471] B. Bacterial Constructs:

[0472] PGEX Constructs: To generate recombinant 151P3D4 proteins inbacteria that are fused to the Glutathione S-transferase (GST) protein,all or parts of the 151P3D4 cDNA protein coding sequence are cloned intothe pGEX family of GST-fusion vectors (Amersham Pharmacia Biotech,Piscataway, N.J.). These constructs allow controlled expression ofrecombinant 151P3D4 protein sequences with GST fused at theamino-terminus and a six histidine epitope (6X His) at thecarboxyl-terminus. The GST and 6X His tags permit purification of therecombinant fusion protein from induced bacteria with the appropriateaffinity matrix and allow recognition of the fusion protein withanti-GST and anti-His antibodies. The 6X His tag is generated by adding6 histidine codons to the cloning primer at the 3′ end, e.g., of theopen reading frame (ORF). A proteolytic cleavage site, such as thePreScission™ recognition site in pGEX-6P-1, may be employed such that itpermits cleavage of the GST tag from 151P3D4-related protein. Theampicillin resistance gene and pBR322 origin permits selection andmaintenance of the pGEX plasmids in E. coli.

[0473] pMAL Constructs: To generate, in bacteria, recombinant 151P3D4proteins that are fused to maltose-binding protein (MBP), all or partsof the 151P3D4 cDNA protein coding sequence are fused to the MBP gene bycloning into the pMAL-c2X and pMAL-p2X vectors (New England Biolabs,Beverly, Mass.). These constructs allow controlled expression ofrecombinant 151P3D4 protein sequences with MBP fused at theamino-terminus and a 6X His epitope tag at the carboxyl-terminus. TheMBP and 6X His tags permit purification of the recombinant protein frominduced bacteria with the appropriate affinity matrix and allowrecognition of the fusion protein with anti-MBP and anti-His antibodies.The 6X His epitope tag is generated by adding 6 histidine codons to the3′ cloning primer. A Factor Xa recognition site permits cleavage of thepMAL tag from 151P3D4. The pMAL-c2X and pMAL-p2X vectors are optimizedto express the recombinant protein in the cytoplasm or periplasmrespectively. Periplasm expression enhances folding of proteins withdisulfide bonds.

[0474] pET Constructs: To express 151P3D4 in bacterial cells, all orparts of the 151P3D4 cDNA protein coding sequence are cloned into thepET family of vectors (Novagen, Madison, Wis.). These vectors allowtightly controlled expression of recombinant 151P3D4 protein in bacteriawith and without fusion to proteins that enhance solubility, such asNusA and thioredoxin (Trx), and epitope tags, such as 6X His and S-Tag™that aid purification and detection of the recombinant protein. Forexample, constructs are made utilizing pET NusA fusion system 43.1 suchthat regions of the 151P3D4 protein are expressed as amino-terminalfusions to NusA.

[0475] C. Yeast Constructs:

[0476] pESC Constructs: To express 151P3D4 in the yeast speciesSaccharomyces cerevisiae for generation of recombinant protein andfunctional studies, all or parts of the 151P3D4 cDNA protein codingsequence are cloned into the pESC family of vectors each of whichcontain 1 of 4 selectable markers, HIS3, TRP1, LEU2, and URA3(Stratagene, La Jolla, Calif.). These vectors allow controlledexpression from the same plasmid of up to 2 different genes or clonedsequences containing either Flag™ or Myc epitope tags in the same yeastcell. This system is useful to confirm protein-protein interactions of151P3D4. In addition, expression in yeast yields similarpost-translational modifications, such as glycosylations andphosphorylations, that are found when expressed in eukaryotic cells.

[0477] pESP Constructs: To express 151P3D4 in the yeast speciesSaccharomyces pombe, all or parts of the 151P3D4 cDNA protein codingsequence are cloned into the pESP family of vectors. These vectors allowcontrolled high level of expression of a 151P3D4 protein sequence thatis fused at either the amino terminus or at the carboxyl terminus to GSTwhich aids purification of the recombinant protein. A Flag™ epitope tagallows detection of the recombinant protein with anti-Flag™ antibody.

Example 8

[0478] Production of Recombinant 151P3D4 in Eukaryotic Systems

[0479] A. Mammalian Constructs:

[0480] To express recombinant 151P3D4 in eukaryotic cells, the full orpartial length 151P3D4 cDNA sequences can be cloned into any one of avariety of expression vectors known in the art. One or more of thefollowing regions of 151P3D4 are expressed in these constructs, aminoacids 1 to 354 of 151P3D4 v.1, amino acids 1 to 721 of 151P3D4v.2, orany 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24,25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42,43, 44, 45, 46, 47, 48, 49, 50 or more contiguous amino acids from151P3D4, variants, or analogs thereof. In certain embodiments a regionof a specific variant of 151P3D4 is expressed that encodes an amino acidat a specific position which differs from the amino acid of any othervariant found at that position. In other embodiments, a region of avariant of 151P3D4 is expressed that lies partly or entirely within asequence that is unique to that variant.

[0481] The constructs can be transfected into any one of a wide varietyof mammalian cells such as 293T cells. Transfected 293T cell lysates canbe probed with the anti-151P3D4 polyclonal serum, described herein.

[0482] pcDNA4/HisMax Constructs: To express 151P3D4 in mammalian cells,a 151P3D4 ORF, or portions thereof, of 151P3D4 are cloned intopcDNA4/HisMax Version A (Invitrogen, Carlsbad, Calif.). Proteinexpression is driven from the cytomegalovirus (CMV) promoter and theSP16 translational enhancer. The recombinant protein has Xpress™ and sixhistidine (6X His) epitopes fused to the amino-terminus. ThepcDNA4/HisMax vector also contains the bovine growth hormone (BGH)polyadenylation signal and transcription termination sequence to enhancemRNA stability along with the SV40 origin for episomal replication andsimple vector rescue in cell lines expressing the large T antigen. TheZeocin resistance gene allows for selection of mammalian cellsexpressing the protein and the ampicillin resistance gene and ColE1origin permits selection and maintenance of the plasmid in E. coli.

[0483] DcDNA3.1/MycHis Constructs: To express 151P3D4 in mammaliancells, a 151P3D4 ORF, or portions thereof, of 151P3D4 with a consensusKozak translation initiation site was cloned into pcDNA3.1/MycHisVersion A (Invitrogen, Carlsbad, Calif.). Protein expression is drivenfrom the cytomegalovirus (CMV) promoter. The recombinant protein has themyc epitope and 6X His epitope fused to the carboxyl-terminus. ThepcDNA3.1/MycHis vector also contains the bovine growth hormone (BGH)polyadenylation signal and transcription termination sequence to enhancemRNA stability, along with the SV40 origin for episomal replication andsimple vector rescue in cell lines expressing the large T antigen. TheNeomycin resistance gene was used, as it allows for selection ofmammalian cells expressing the protein and the ampicillin resistancegene and ColEI origin permits selection and maintenance of the plasmidin E. coli. Results of expression from 151P3D4.pcDNA3.1/MycHis constructare shown in FIG. 20.

[0484] PcDNA3.1/CT-GFP-TOPO Construct: To express 151P3D4 in mammaliancells and to allow detection of the recombinant proteins usingfluorescence, a 151P3D4 ORF, or portions thereof, with a consensus Kozaktranslation initiation site are cloned into pcDNA3.1/CT-GFP-TOPO(Invitrogen, Calif.). Protein expression is driven from thecytomegalovirus (CMV) promoter. The recombinant proteins have the GreenFluorescent Protein (GFP) fused to the carboxyl-terminus facilitatingnon-invasive, in vivo detection and cell biology studies. ThepcDNA3.1CT-GFP-TOPO vector also contains the bovine growth hormone (BGH)polyadenylation signal and transcription termination sequence to enhancemRNA stability along with the SV40 origin for episomal replication andsimple vector rescue in cell lines expressing the large T antigen. TheNeomycin resistance gene allows for selection of mammalian cells thatexpress the protein, and the ampicillin resistance gene and ColE1 originpermits selection and maintenance of the plasmid in E. coli. Additionalconstructs with an amino-terminal GFP fusion are made inpcDNA3.1/NT-GFP-TOPO spanning the entire length of a 151P3D4 protein.

[0485] PAPtag: A 151P3D4 ORF, or portions thereof, is cloned intopAPtag-5 (GenHunter Corp. Nashville, Tenn.). This construct generates analkaline phosphatase fusion at the carboxyl-terminus of a 151P3D4protein while fusing the IgGκ signal sequence to the amino-terminus.Constructs are also generated in which alkaline phosphatase with anamino-terminal IgGκ signal sequence is fused to the amino-terminus of a151P3D4 protein. The resulting recombinant 151P3D4 proteins areoptimized for secretion into the media of transfected mammalian cellsand can be used to identify proteins such as ligands or receptors thatinteract with 151P3D4 proteins. Protein expression is driven from theCMV promoter and the recombinant proteins also contain myc and 6X Hisepitopes fused at the carboxyl-terminus that facilitates detection andpurification. The Zeocin resistance gene present in the vector allowsfor selection of mammalian cells expressing the recombinant protein andthe ampicillin resistance gene permits selection of the plasmid in E.coli.

[0486] ptag5: A 151P3D4 ORF, or portions thereof, is cloned into pTag-5.This vector is similar to pAPtag but without the alkaline phosphatasefusion. This construct generates 151P3D4 protein with an amino-terminalIgGκ signal sequence and myc and 6X His epitope tags at thecarboxyl-terminus that facilitate detection and affinity purification.The resulting recombinant 151P3D4 protein is optimized for secretioninto the media of transfected mammalian cells, and is used as immunogenor ligand to identify proteins such as ligands or receptors thatinteract with the 151P3D4 proteins. Protein expression is driven fromthe CMV promoter. The Zeocin resistance gene present in the vectorallows for selection of mammalian cells expressing the protein, and theampicillin resistance gene permits selection of the plasmid in E. coli.

[0487] PsecFc: A 151P3D4 ORF, or portions thereof, is also cloned intopsecFc. The psecFc vector was assembled by cloning the humanimmunoglobulin G1 (IgG) Fc (hinge, CH2, CH3 regions) into pSecTag2(Invitrogen, Calif.). This construct generates an IgG1 Fc fusion at thecarboxyl-terminus of the 151P3D4 proteins, while fusing the IgGK signalsequence to N-terminus. 151P3D4 fusions utilizing the murine IgG1 Fcregion are also used. The resulting recombinant 151P3D4 proteins areoptimized for secretion into the media of transfected mammalian cells,and can be used as immunogens or to identify proteins such as ligands orreceptors that interact with 151P3D4 protein. Protein expression isdriven from the CMV promoter. The hygromycin resistance gene present inthe vector allows for selection of mammalian cells that express therecombinant protein, and the ampicillin resistance gene permitsselection of the plasmid in E. coli.

[0488] pSRα Constructs: To generate mammalian cell lines that express151P3D4 constitutively, 151P3D4 ORF, or portions thereof, of 151P3D4 arecloned into pSRα constructs. Amphotropic and ecotropic retroviruses aregenerated by transfection of pSRα constructs into the 293T-10A1packaging line or co-transfection of pSRα and a helper plasmid(containing deleted packaging sequences) into the 293 cells,respectively. The retrovirus is used to infect a variety of mammaliancell lines, resulting in the integration of the cloned gene, 151P3D4,into the host cell-lines. Protein expression is driven from a longterminal repeat (LTR). The Neomycin resistance gene present in thevector allows for selection of mammalian cells that express the protein,and the ampicillin resistance gene and ColE1 origin permit selection andmaintenance of the plasmid in E. coli. The retroviral vectors canthereafter be used for infection and generation of various cell linesusing, for example, PC3, NIH 3T3, TsuPr1, 293 or rat-1 cells.

[0489] Additional pSRα constructs are made that fuse an epitope tag suchas the FLAG™ tag to the carboxyl-terminus of 151P3D4 sequences to allowdetection using anti-Flag antibodies. For example, the FLAG™ sequence 5′gat tac aag gat gac gac gat aag 3′ (SEQ ID NO:______) is added tocloning primer at the 3′ end of the ORF. Additional pSRα constructs aremade to produce both amino-terminal and carboxyl-terminal GFP and myc/6XHis fusion proteins of the full-length 151P3D4 proteins.

[0490] Additional Viral Vectors: Additional constructs are made forviral-mediated delivery and expression of 151P3D4. High virus titerleading to high level expression of 151P3D4 is achieved in viraldelivery systems such as adenoviral vectors and herpes amplicon vectors.A 151P3D4 coding sequences or fragments thereof are amplified by PCR andsubcloned into the AdEasy shuttle vector (Stratagene). Recombination andvirus packaging are performed according to the manufacturer'sinstructions to generate adenoviral vectors. Alternatively, 151P3D4coding sequences or fragments thereof are cloned into the HSV-1 vector(Imgenex) to generate herpes viral vectors. The viral vectors arethereafter used for infection of various cell lines such as PC3, NIH3T3, 293 or rat-1 cells.

[0491] Regulated Expression Systems: To control expression of 151P3D4 inmammalian cells, coding sequences of 151P3D4, or portions thereof, arecloned into regulated mammalian expression systems such as the T-RexSystem (Invitrogen), the GeneSwitch System (Invitrogen) and thetightly-regulated Ecdysone System (Sratagene). These systems allow thestudy of the temporal and concentration dependent effects of recombinant151P3D4. These vectors are thereafter used to control expression of151P3D4 in various cell lines such as PC3, NIH 3T3, 293 or rat-1 cells.

[0492] B. Baculovirus Expression Systems

[0493] To generate recombinant 151P3D4 proteins in a baculovirusexpression system, 151P3D4 ORF, or portions thereof, are cloned into thebaculovirus transfer vector pBlueBac 4.5 (Invitrogen), which provides aHis-tag at the N-terminus. Specifically, pBlueBac-151P3D4 isco-transfected with helper plasmid pBac-N-Blue (Invitrogen) into SF9(Spodoptera frugiperda) insect cells to generate recombinant baculovirus(see Invitrogen instruction manual for details). Baculovirus is thencollected from cell supernatant and purified by plaque assay.

[0494] Recombinant 151P3D4 protein is then generated by infection ofHighFive insect cells (Invitrogen) with purified baculovirus.Recombinant 151P3D4 protein can be detected using anti-151P3D4 oranti-His-tag antibody. 151P3D4 protein can be purified and used invarious cell-based assays or as immunogen to generate polyclonal andmonoclonal antibodies specific for 151P3D4.

Example 9

[0495] Antigenicity Profiles and Secondary Structure

[0496] FIGS. 5(A & B), FIGS. 6(A & B), FIGS. 7(A & B), FIGS. 8(A & B),and FIGS. 9(A & B) depict graphically five amino acid profiles of151P3D4 variants 1 and 2, each assessment available by accessing theProtScale website (URL www.expasy.ch/cgi-bin/protscale.pl) on the ExPasymolecular biology server.

[0497] These profiles: FIG. 5, Hydrophilicity, (Hopp T. P., Woods K. R.,1981. Proc. Natl. Acad. Sci. U.S.A. 78:3824-3828); FIG. 6,Hydropathicity, (Kyte J., Doolittle R. F., 1982. J. Mol. Biol.157:105-132); FIG. 7, Percentage Accessible Residues (Janin J., 1979Nature 277:491-492); FIG. 8, Average Flexibility, (Bhaskaran R., andPonnuswamy P. K., 1988. Int. J. Pept. Protein Res. 32:242-255); FIG. 9,Beta-turn (Deleage, G., Roux B. 1987 Protein Engineering 1:289-294); andoptionally others available in the art, such as on the ProtScalewebsite, were used to identify antigenic regions of the 151P3D4 protein.Each of the above amino acid profiles of 151P3D4 were generated usingthe following ProtScale parameters for analysis: 1) A window size of 9;2) 100% weight of the window edges compared to the window center; and,3) amino acid profile values normalized to lie between 0 and 1.

[0498] Hydrophilicity (FIG. 5), Hydropathicity (FIG. 6) and PercentageAccessible Residues (FIG. 7) profiles were used to determine stretchesof hydrophilic amino acids (i.e., values greater than 0.5 on theHydrophilicity and Percentage Accessible Residues profile, and valuesless than 0.5 on the Hydropathicity profile). Such regions are likely tobe exposed to the aqueous environment, be present on the surface of theprotein, and thus available for immune recognition, such as byantibodies.

[0499] Average Flexibility (FIG. 8) and Beta-turn (FIG. 9) profilesdetermine stretches of amino acids (i.e., values greater than 0.5 on theBeta-turn profile and the Average Flexibility profile) that are notconstrained in secondary structures such as beta sheets and alphahelices. Such regions are also more likely to be exposed on the proteinand thus accessible to immune recognition, such as by antibodies.

[0500] Antigenic sequences of the 151P3D4 variant proteins indicated,e.g., by the profiles set forth in FIGS. 5(A & B), FIGS. 6(A & B), FIGS.7(A & B), FIGS. 8(A & B), and/or FIGS. 9(A & B) are used to prepareimmunogens, either peptides or nucleic acids that encode them, togenerate therapeutic and diagnostic anti-151P3D4 antibodies. Theimmunogen can be any 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18,19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, 50 or more than 50contiguous amino acids, or the corresponding nucleic acids that encodethem, from the 151P3D4 protein variants 1 and 2 listed in FIGS. 2 and 3.In particular, peptide immunogens of the invention can comprise, apeptide region of at least 5 amino acids of FIGS. 2 and 3 in any wholenumber increment that includes an amino acid position having a valuegreater than 0.5 in the Hydrophilicity profiles of FIG. 5; a peptideregion of at least 5 amino acids of FIGS. 2 and 3 in any whole numberincrement that includes an amino acid position having a value less than0.5 in the Hydropathicity profile of FIG. 6; a peptide region of atleast 5 amino acids of FIGS. 2 and 3 in any whole number increment thatincludes an amino acid position having a value greater than 0.5 in thePercent Accessible Residues profiles of FIG. 7; a peptide region of atleast 5 amino acids of FIGS. 2 and 3 in any whole number increment thatincludes an amino acid position having a value greater than 0.5 in theAverage Flexibility profiles on FIG. 8; and, a peptide region of atleast 5 amino acids of FIGS. 2 and 3 in any whole number increment thatincludes an amino acid position having a value greater than 0.5 in theBeta-turn profile of FIGS. 9. Peptide immunogens of the invention canalso comprise nucleic acids that encode any of the forgoing.

[0501] All immunogens of the invention, peptide or nucleic acid, can beembodied in human unit dose form, or comprised by a composition thatincludes a pharmaceutical excipient compatible with human physiology.

[0502] The secondary structure of 151P3D4 protein variants 1 and 2,namely the predicted presence and location of alpha helices, extendedstrands, and random coils, is predicted from the primary amino acidsequence using the HNN—Hierarchical Neural Network method (Guermeur,1997, http://pbil.ibcp.fr/cgi-bin/npsa_automat.pl 1?page=npsa_nn.html),accessed from the ExPasy molecular biology server(http://www.expasy.ch/tools/). The analysis indicates that 151P3D4variant 1 is composed of 25.71% alpha helix, 21.47% extended strand, and52.82% random coil (FIG. 13A). Variant 2 is composed of 25.80% alphahelix, 16.64% extended strand, and 57.56% random coil (FIG. 13B).

[0503] Analysis for the potential presence of transmembrane domains inthe 151P3D4 variant proteins was carried out using a variety oftransmembrane prediction algorithms accessed from the ExPasy molecularbiology server (http://www.expasy.ch/tools/). The programs do notpredict the presence of transmembrane domains in the 151P3D4 proteinvariants, suggesting that they are soluble proteins.

Example 10

[0504] Generation of 151P3D4 Polyclonal Antibodies

[0505] Polyclonal antibodies can be raised in a mammal, for example, byone or more injections of an immunizing agent and, if desired, anadjuvant. Typically, the immunizing agent and/or adjuvant will beinjected in the mammal by multiple subcutaneous or intraperitonealinjections. In addition to immunizing with a full length 151P3D4 proteinvariant, computer algorithms are employed in design of immunogens that,based on amino acid sequence analysis contain characteristics of beingantigenic and available for recognition by the immune system of theimmunized host (see the Example entitled “Antigenicity Profiles”). Suchregions would be predicted to be hydrophilic, flexible, in beta-turnconformations, and be exposed on the surface of the protein (see, e.g.,FIGS. 5(A & B), FIGS. 6(A & B), FIGS. 7(A & B), FIGS. 8(A & B), or FIGS.9(A & B) for amino acid profiles that indicate such regions of 151P3D4protein variants).

[0506] For example, recombinant bacterial fusion proteins or peptidescontaining hydrophilic, flexible, beta-turn regions of 151P3D4 proteinvariants are used as antigens to generate polyclonal antibodies in NewZealand White rabbits. For example, in 151P3D4 variant 1, such regionsinclude, but are not limited to, amino acids 99-151, amino acids218-249, and amino acids 311-332. In sequence specific for variant 2,such regions include, but are not limited to, amino acids 16-38, aminoacids 76-90, amino acids 182-230, and amino acids 383-400. It is usefulto conjugate the immunizing agent to a protein known to be immunogenicin the mammal being immunized. Examples of such immunogenic proteinsinclude, but are not limited to, keyhole limpet hemocyanin (KLH), serumalbumin, bovine thyroglobulin, and soybean trypsin inhibitor. In oneembodiment, a peptide encoding amino acids 311-332 of 151P3D4 variant 1is conjugated to KLH and used to immunize the rabbit. Alternatively theimmunizing agent may include all or portions of the 151P3D4 variantproteins, analogs or fusion proteins thereof. For example, the 151P3D4variant 1 amino acid sequence can be fused using recombinant DNAtechniques to any one of a variety of fusion protein partners that arewell known in the art, such as glutathione-S-transferase (GST) and HIStagged fusion proteins. Such fusion proteins are purified from inducedbacteria using the appropriate affinity matrix.

[0507] In one embodiment, a GST-fusion protein encoding the N-terminalregion of 151P3D4 variant 1, amino acids 16-150, minus the first 15amino acids that likely encodes a cleavable signal peptide, is producedand purified and used as immunogen. Other recombinant bacterial fusionproteins that may be employed include maltose binding protein, LacZ,thioredoxin, NusA, or an immunoglobulin constant region (see the sectionentitled “Production of 151P3D4 in Prokaryotic Systems” and CurrentProtocols In Molecular Biology, Volume 2, Unit 16, Frederick M. Ausubulet al. eds., 1995; Linsley, P. S., Brady, W., Urnes, M., Grosmaire, L.,Damle, N., and Ledbetter, L.(1991) J.Exp. Med. 174, 561-566).

[0508] In addition to bacterial derived fusion proteins, mammalianexpressed protein antigens are also used. These antigens are expressedfrom mammalian expression vectors such as the Tag5 and Fc-fusion vectors(see the section entitled “Production of Recombinant 151P3D4 inEukaryotic Systems”), and retain post-translational modifications suchas glycosylations found in native protein. In one embodiment, aminoacids 16-354 of variant 1, minus the endogenous signal peptide, iscloned into the Tag5 mammalian secretion vector. The recombinant proteinis purified by metal chelate chromatography from tissue culturesupernatants of 293T cells stably expressing the recombinant vector. Thepurified Tag5 151P3D4 protein is then used as immunogen.

[0509] During the immunization protocol, it is useful to mix or emulsifythe antigen in adjuvants that enhance the immune response of the hostanimal. Examples of adjuvants include, but are not limited to, completeFreund's adjuvant (CFA) and MPL-TDM adjuvant (monophosphoryl Lipid A,synthetic trehalose dicorynomycolate).

[0510] In a typical protocol, rabbits are initially immunizedsubcutaneously with up to 200 μg, typically 100-200 μg, of fusionprotein or peptide conjugated to KLH mixed in complete Freund's adjuvant(CFA). Rabbits are then injected subcutaneously every two weeks with upto 200 μg, typically 100-200 μg, of the immunogen in incomplete Freund'sadjuvant (IFA). Test bleeds are taken approximately 7-10 days followingeach immunization and used to monitor the titer of the antiserum byELISA.

[0511] To test reactivity and specificity of immune serum, such as therabbit serum derived from immunization with the Tag5-151P3D4 variant 1protein, the full-length 151P3D4 variant 1 cDNA is cloned into pCDNA 3.1myc-his expression vector (Invitrogen, see the Example entitled“Production of Recombinant 151P3D4 in Eukaryotic Systems”). Aftertransfection of the constructs into 293T cells, cell lysates are probedwith the anti-151P3D4 serum and with anti-His antibody (Santa CruzBiotechnologies, Santa Cruz, Calif.) to determine specific reactivity todenatured 151P3D4 protein using the Western blot technique (FIG. 20)shows expression of Myc His epitope tagged 151P3D4 variant 1 protein in293T cells as detected by an anti-His antibody. In addition, the immuneserum is tested by fluorescence microscopy, flow cytometry andimmunoprecipitation against 293T and other recombinant151P3D4-expressing cells to determine specific recognition of nativeprotein. Western blot, immunoprecipitation, fluorescent microscopy, andflow cytometric techniques using cells that endogenously express 151P3D4are also carried out to test reactivity and specificity.

[0512] Anti-serum from rabbits immunized with 151P3D4 variant fusionproteins, such as GST and MBP fusion proteins, are purified by depletionof antibodies reactive to the fusion partner sequence by passage over anaffinity column containing the fusion partner either alone or in thecontext of an irrelevant fusion protein. For example, antiserum derivedfrom a GST-151P3D4 variant 1 fusion protein encoding amino acids 16-150is first purified by passage over a column of GST protein covalentlycoupled to AffiGel matrix (BioRad, Hercules, Calif.). The antiserum isthen affinity purified by passage over a column composed of a MBP-fusionprotein also encoding amino acids 16-150 covalently coupled to AffiGelmatrix. The serum is then further purified by protein G affinitychromatography to isolate the IgG fraction. Sera from other His-taggedantigens and peptide immunized rabbits as well as fusion partnerdepleted sera are affinity purified by passage over a column matrixcomposed of the original protein immunogen or free peptide.

Example 11

[0513] Generation of 151P3D4 Monoclonal Antibodies (mAbs)

[0514] In one embodiment, therapeutic mAbs to 151P3D4 variants comprisethose that react with epitopes specific for each variant protein orspecific to sequences in common between the variants that would disruptor modulate the biological function of the 151P3D4 variants, for examplethose that would disrupt the interaction with ligands and bindingpartners. Immunogens for generation of such mAbs include those designedto encode or contain the entire 151P3D4 protein variant sequence,regions of the 151P3D4 protein variants predicted to be antigenic fromcomputer analysis of the amino acid sequence (see, e.g., FIGS. 5(A & B),FIGS. 6(A & B), FIGS. 7(A & B), FIGS. 8(A & B), or FIGS. 9(A & B), andthe Example entitled “Antigenicity Profiles”). Immunogens includepeptides, recombinant bacterial proteins, and mammalian expressed Tag 5proteins and human and murine IgG FC fusion proteins. In addition, cellsengineered to express high levels of a respective 151P3D4 variant, suchas 293T-151P3D4 variant 1 or 300.19-151P3D4 variant lmurine Pre-B cells,are used to immunize mice.

[0515] To generate mAbs to a 151P3D4 variant, mice are first immunizedintraperitoneally (IP) with, typically, 10-50 μg of protein immunogen or10⁷ 151P3D4-expressing cells mixed in complete Freund's adjuvant. Miceare then subsequently immunized IP every 2-4 weeks with, typically,10-50 μg of protein immunogen or 10⁷ cells mixed in incomplete Freund'sadjuvant. Alternatively, MPL-TDM adjuvant is used in immunizations. Inaddition to the above protein and cell-based immunization strategies, aDNA-based immunization protocol is employed in which a mammalianexpression vector encoding a 151P3D4 variant sequence is used toimmunize mice by direct injection of the plasmid DNA. For example, aminoacids 16-354 is cloned into the Tag5 mammalian secretion vector and therecombinant vector is used as immunogen. In another example the sameamino acids are cloned into an Fc-fusion secretion vector in which the151P3D4 variant 1 sequence is fused at the amino-terminus to an IgKleader sequence and at the carboxyl-terminus to the coding sequence ofthe human or murine IgG Fc region. This recombinant vector is then usedas immunogen. The plasmid immunization protocols are used in combinationwith purified proteins expressed from the same vector and with cellsexpressing the respective 151P3D4 variant.

[0516] During the immunization protocol, test bleeds are taken 7-10 daysfollowing an injection to monitor titer and specificity of the immuneresponse. Once appropriate reactivity and specificity is obtained asdetermined by ELISA, Western blotting, immunoprecipitation, fluorescencemicroscopy, and flow cytometric analyses, fusion and hybridomageneration is then carried out with established procedures well known inthe art (see, e.g., Harlow and Lane, 1988).

[0517] In one embodiment for generating 151P3D4 monoclonal antibodies, aTag5-151P3D4 variant 1 antigen encoding amino acids 16-354, is expressedand purified from stably transfected 293T cells. Balb C mice areinitially immunized intraperitoneally with 25 μg of the Tag5-151P3D4variant 1 protein mixed in complete Freund's adjuvant. Mice aresubsequently immunized every two weeks with 25 μg of the antigen mixedin incomplete Freund's adjuvant for a total of three immunizations.ELISA using the Tag5 antigen determines the titer of serum fromimmunized mice. Reactivity and specificity of serum to full length151P3D4 variant 1 protein is monitored by Western blotting,immunoprecipitation and flow cytometry using 293T cells transfected withan expression vector encoding the 151P3D4 variant 1 cDNA (see e.g., theExample entitled “Production of Recombinant 151P3D4 in EukaryoticSystems” and FIG. 20. Other recombinant 151P3D4 variant 1-expressingcells or cells endogenously expressing 151P3D4 variant 1 are also used.Mice showing the strongest reactivity are rested and given a finalinjection of Tag5 antigen in PBS and then sacrificed four days later.The spleens of the sacrificed mice are harvested and fused to SPO/2myeloma cells using standard procedures (Harlow and Lane, 1988).Supernatants from HAT selected growth wells are screened by ELISA,Western blot, immunoprecipitation, fluorescent microscopy, and flowcytometry to identify 151P3D4 specific antibody-producing clones.

[0518] In another embodiment, a Tag5 antigen encoding amino acids 1-400of variant 2 is produced, purified and used as immunogen to derivemonoclonal antibodies specific to 151P3D4 variant 2. Hybridomasupernatants are then screened on both 151P3D4 variant 2- and 151P3D4variant 1-expressing cells to identify specific anti-151P3D4 variant 2monoclonal antibodies.

[0519] The binding affinity of a 151P3D4 monoclonal antibody isdetermined using standard technologies. Affinity measurements quantifythe strength of antibody to epitope binding and are used to help definewhich 151P3D4 monoclonal antibodies preferred for diagnostic ortherapeutic use, as appreciated by one of skill in the art. The BIAcoresystem (Uppsala, Sweden) is a preferred method for determining bindingaffinity. The BIAcore system uses surface plasmon resonance (SPR,Welford K. 1991, Opt. Quant. Elect. 23:1; Morton and Myszka, 1998,Methods in Enzymology 295: 268) to monitor biomolecular interactions inreal time. BIAcore analysis conveniently generates association rateconstants, dissociation rate constants, equilibrium dissociationconstants, and affinity constants.

Example 12

[0520] HLA Class I and Class II Binding Assays

[0521] HLA class I and class II binding assays using purified HLAmolecules are performed in accordance with disclosed protocols (e.g.,PCT publications WO 94/20127 and WO 94/03205; Sidney et al., CurrentProtocols in Immunology 18.3.1 (1998); Sidney, et al., J. Immunol.154:247 (1995); Sette, et al., Mol. Immunol. 31:813 (1994)). Briefly,purified MHC molecules (5 to 500 nM) are incubated with variousunlabeled peptide inhibitors and 1-10 nM ¹²⁵I-radiolabeled probepeptides as described. Following incubation, MHC-peptide complexes areseparated from free peptide by gel filtration and the fraction ofpeptide bound is determined. Typically, in preliminary experiments, eachMHC preparation is titered in the presence of fixed amounts ofradiolabeled peptides to determine the concentration of HLA moleculesnecessary to bind 10-20% of the total radioactivity. All subsequentinhibition and direct binding assays are performed using these HLAconcentrations.

[0522] Since under these conditions [label]<[HLA] and IC₅₀≧[HLA], themeasured IC₅₀ values are reasonable approximations of the true K_(D)values. Peptide inhibitors are typically tested at concentrationsranging from 120 μg/ml to 1.2 ng/ml, and are tested in two to fourcompletely independent experiments. To allow comparison of the dataobtained in different experiments, a relative binding figure iscalculated for each peptide by dividing the IC₅₀ of a positive controlfor inhibition by the IC₅₀ for each tested peptide (typically unlabeledversions of the radiolabeled probe peptide). For database purposes, andinter-experiment comparisons, relative binding values are compiled.These values can subsequently be converted back into IC₅₀ nM values bydividing the IC₅₀ nM of the positive controls for inhibition by therelative binding of the peptide of interest. This method of datacompilation is accurate and consistent for comparing peptides that havebeen tested on different days, or with different lots of purified MHC.

[0523] Binding assays as outlined above may be used to analyze HLAsupermotif and/or HLA motif-bearing peptides (see Table IV).

Example 13

[0524] Identification of HLA Supermotif- and Motif-Bearing CTL CandidateEpitopes

[0525] HLA vaccine compositions of the invention can include multipleepitopes. The multiple epitopes can comprise multiple HLA supermotifs ormotifs to achieve broad population coverage. This example illustratesthe identification and confirmation of supermotif- and motif-bearingepitopes for the inclusion in such a vaccine composition. Calculation ofpopulation coverage is performed using the strategy described below.

[0526] Computer Searches and Algorithms for Identification of Supermotifand/or Motif-Bearing Epitopes

[0527] The searches performed to identify the motif-bearing peptidesequences in the Example entitled “Antigenicity Profiles” and TablesV-XVIII and XXII-LI employ the protein sequence data from the geneproduct of 151P3D4 set forth in FIGS. 2 and 3.

[0528] Computer searches for epitopes bearing HLA Class I or Class IIsupermotifs or motifs are performed as follows. All translated 151P3D4protein sequences are analyzed using a-text string search softwareprogram to identify potential peptide sequences containing appropriateHLA binding motifs; such programs are readily produced in accordancewith information in the art in view of known motif/supermotifdisclosures. Furthermore, such calculations can be made mentally.

[0529] Identified A2-, A3-, and DR-supermotif sequences are scored usingpolynomial algorithms to predict their capacity to bind to specificHLA-Class I or Class II molecules. These polynomial algorithms accountfor the impact of different amino acids at different positions, and areessentially based on the premise that the overall affinity (or ΔG) ofpeptide-HLA molecule interactions can be approximated as a linearpolynomial function of the type:

“ΔG”=a _(1i) ×a _(2i) ×a _(3i) . . . ×a _(ni)

[0530] where a_(ji) is a coefficient which represents the effect of thepresence of a given amino acid (j) at a given position (i) along thesequence of a peptide of n amino acids. The crucial assumption of thismethod is that the effects at each position are essentially independentof each other (i.e., independent binding of individual side-chains).When residue j occurs at position i in the peptide, it is assumed tocontribute a constant amount j_(i) to the free energy of binding of thepeptide irrespective of the sequence of the rest of the peptide.

[0531] The method of derivation of specific algorithm coefficients hasbeen described in Gulukota et al., J. Mol. Biol. 267:1258-126, 1997;(see also Sidney et al., Human Immunol. 45:79-93, 1996; and Southwood etal., J. Immunol. 160:3363-3373, 1998). Briefly, for all i positions,anchor and non-anchor alike, the geometric mean of the average relativebinding (ARB) of all peptides carrying j is calculated relative to theremainder of the group, and used as the estimate of j_(i). For Class IIpeptides, if multiple alignments are possible, only the highest scoringalignment is utilized, following an iterative procedure. To calculate analgorithm score of a given peptide in a test set, the ARB valuescorresponding to the sequence of the peptide are multiplied. If thisproduct exceeds a chosen threshold, the peptide is predicted to bind.Appropriate thresholds are chosen as a function of the degree ofstringency of prediction desired.

[0532] Selection of HLA-A2 Supertype Cross-Reactive Peptides

[0533] Protein sequences from 151P3D4 are scanned utilizing motifidentification software, to identify 8-, 9- 10- and 11-mer sequencescontaining the HLA-A2-supermotif main anchor specificity. Typically,these sequences are then scored using the protocol described above andthe peptides corresponding to the positive-scoring sequences aresynthesized and tested for their capacity to bind purified HLA-A*0201molecules in vitro (HLA-A*0201 is considered a prototype A2 supertypemolecule).

[0534] These peptides are then tested for the capacity to bind toadditional A2-supertype molecules (A*0202, A*0203, A*0206, and A*6802).Peptides that bind to at least three of the five A2-supertype allelestested are typically deemed A2-supertype cross-reactive binders.Preferred peptides bind at an affinity equal to or less than 500 nM tothree or more HLA-A2 supertype molecules.

[0535] Selection of HLA-A3 Supermotif-Bearing Epitopes

[0536] The 151P3D4 protein sequence(s) scanned above is also examinedfor the presence of peptides with the HLA-A3-supermotif primary anchors.Peptides corresponding to the HLA A3 supermotif-bearing sequences arethen synthesized and tested for binding to HLA-A*0301 and HLA-A*1101molecules, the molecules encoded by the two most prevalent A3-supertypealleles. The peptides that bind at least one of the two alleles withbinding affinities of ≦500 nM, often ≦200 nM, are then tested forbinding cross-reactivity to the other common A3-supertype alleles (e.g.,A*3101, A*3301, and A*6801) to identify those that can bind at leastthree of the five HLA-A3-supertype molecules tested.

[0537] Selection of HLA-B7 Supermotif Bearing Epitopes

[0538] The 151P3D4 protein(s) scanned above is also analyzed for thepresence of 8-, 9- 10-, or 11-mer peptides with the HLA-B7-supermotif.Corresponding peptides are synthesized and tested for binding toHLA-B*0702, the molecule encoded by the most common B7-supertype allele(i.e., the prototype B7 supertype allele). Peptides binding B*0702 withIC₅₀ of ≦500 nM are identified using standard methods. These peptidesare then tested for binding to other common B7-supertype molecules(e.g., B*3501, B*5101, B*5301, and B*5401). Peptides capable of bindingto three or more of the five B7-supertype alleles tested are therebyidentified.

[0539] Selection of A1 and A24 Motif-Bearing Epitopes

[0540] To further increase population coverage, HLA-A 1 and -A24epitopes can also be incorporated into vaccine compositions. An analysisof the 151P3D4 protein can also be performed to identify HLA-A1- andA24-motif-containing sequences.

[0541] High affinity and/or cross-reactive binding epitopes that bearother motif and/or supermotifs are identified using analogousmethodology.

Example 14

[0542] Confirmation of Immunogenicity

[0543] Cross-reactive candidate CTL A2-supermotif-bearing peptides thatare identified as described herein are selected to confirm in vitroimmunogenicity. Confirmation is performed using the followingmethodology:

[0544] Target Cell Lines for Cellular Screening:

[0545] The .221A2.1 cell line, produced by transferring the HLA-A2.1gene into the HLA-A, -B, -C null mutant human B-lymphoblastoid cell line721.221, is used as the peptide-loaded target to measure activity ofHLA-A2.1-restricted CTL. This cell line is grown in RPMI-1640 mediumsupplemented with antibiotics, sodium pyruvate, nonessential amino acidsand 10% (v/v) heat inactivated FCS. Cells that express an antigen ofinterest, or transfectants comprising the gene encoding the antigen ofinterest, can be used as target cells to confirm the ability ofpeptide-specific CTLs to recognize endogenous antigen.

[0546] Primary CTL Induction Cultures:

[0547] Generation of Dendritic Cells (DC): PBMCs are thawed in RPMI with30 μg/ml DNAse, washed twice and resuspended in complete medium(RPMI-1640 plus 5% AB human serum, non-essential amino acids, sodiumpyruvate, L-glutamine and penicillin/streptomycin). The monocytes arepurified by plating 10×10⁶ PBMC/well in a 6-well plate. After 2 hours at37° C., the non-adherent cells are removed by gently shaking the platesand aspirating the supernatants. The wells are washed a total of threetimes with 3 ml RPMI to remove most of the non-adherent and looselyadherent cells. Three ml of complete medium containing 50 ng/ml ofGM-CSF and 1,000 U/ml of IL-4 are then added to each well. TNFα is addedto the DCs on day 6 at 75 ng/ml and the cells are used for CTL inductioncultures on day 7.

[0548] Induction of CTL with DC and Peptide: CD8+ T-cells are isolatedby positive selection with Dynal immunomagnetic beads (Dynabeads® M-450)and the detacha-bead® reagent. Typically about 200-250×10⁶ PBMC areprocessed to obtain 24×10⁶ CD8⁺ T-cells (enough for a 48-well plateculture). Briefly, the PBMCs are thawed in RPMI with 30 μg/ml DNAse,washed once with PBS containing 1% human AB serum and resuspended inPBS/1% AB serum at a concentration of 20×10⁶cells/ml. The magnetic beadsare washed 3 times with PBS/AB serum, added to the cells (140 μlbeads/20×10⁶ cells) and incubated for 1 hour at 4° C. with continuousmixing. The beads and cells are washed 4× with PBS/AB serum to removethe nonadherent cells and resuspended at 100×10⁶ cells/ml (based on theoriginal cell number) in PBS/AB serum containing 100 μl/ml detacha-bead®reagent and 30 μg/ml DNAse. The mixture is incubated for 1 hour at roomtemperature with continuous mixing. The beads are washed again withPBS/AB/DNAse to collect the CD8+ T-cells. The DC are collected andcentrifuged at 1300 rpm for 5-7 minutes, washed once with PBS with 1%BSA, counted and pulsed with 40 μg/ml of peptide at a cell concentrationof 1-2×10⁶/ml in the presence of 3 μg/ml β₂-microglobulin for 4 hours at20° C. The DC are then irradiated (4,200 rads), washed 1 time withmedium and counted again.

[0549] Setting up induction cultures: 0.25 ml cytokine-generated DC (at×10⁵ cells/ml) are co-cultured with 0.25 ml of CD8+ T-cells (at 2×10⁶cell/ml) in each well of a 48-well plate in the presence of 10 ng/ml ofIL-7. Recombinant human IL-10 is added the next day at a finalconcentration of 10 ng/ml and rhuman IL-2 is added 48 hours later at 10IU/ml.

[0550] Restimulation of the induction cultures with peptide-pulsedadherent cells: Seven and fourteen days after the primary induction, thecells are restimulated with peptide-pulsed adherent cells. The PBMCs arethawed and washed twice with RPMI and DNAse. The cells are resuspendedat 5×10⁶ cells/ml and irradiated at ˜4200 rads. The PBMCs are plated at2×10⁶ in 0.5 ml complete medium per well and incubated for 2 hours at37° C. The plates are washed twice with RPMI by tapping the plate gentlyto remove the nonadherent cells and the adherent cells pulsed with 10μg/ml of peptide in the presence of 3 μg/ml β₂ microglobulin in 0.25 mlRPMI/5% AB per well for 2 hours at 37° C. Peptide solution from eachwell is aspirated and the wells are washed once with RPMI. Most of themedia is aspirated from the induction cultures (CD8+ cells) and broughtto 0.5 ml with fresh media. The cells are then transferred to the wellscontaining the peptide-pulsed adherent cells. Twenty four hours laterrecombinant human IL-10 is added at a final concentration of 10 ng/mland recombinant human IL2 is added the next day and again 2-3 days laterat 50 IU/ml (Tsai et al., Critical Reviews in Immunology 18(1-2):65-75,1998). Seven days later, the cultures are assayed for CTL activity in a⁵¹Cr release assay. In some experiments the cultures are assayed forpeptide-specific recognition in the in situ IFNγ ELISA at the time ofthe second restimulation followed by assay of endogenous recognition 7days later. After expansion, activity is measured in both assays for aside-by-side comparison.

[0551] Measurement of CTL Lytic Activity by ⁵¹Cr release.

[0552] Seven days after the second restimulation, cytotoxicity isdetermined in a standard (5 hr) ⁵¹Cr release assay by assayingindividual wells at a single E:T. Peptide-pulsed targets are prepared byincubating the cells with 10 μg/ml peptide overnight at 37° C.

[0553] Adherent target cells are removed from culture flasks withtrypsin-EDTA. Target cells are labeled with 200 μCi of ⁵¹Cr sodiumchromate (Dupont, Wilmington, Del.) for1 hour at 37° C. Labeled targetcells are resuspended at 10⁶ per ml and diluted 1:10 with K562 cells ata concentration of 3.3×10⁶/ml (an NK-sensitive erythroblastoma cell lineused to reduce non-specific lysis). Target cells (100 μl) and effectors(1001 μl) are plated in 96 well round-bottom plates and incubated for 5hours at 37° C. At that time, 100 μl of supernatant are collected fromeach well and percent lysis is determined according to the formula:

[(cpm of the test sample−cpm of the spontaneous ⁵¹Cr releasesample)/(cpm of the maximal ⁵¹Cr release sample−cpm of the spontaneous⁵¹Cr release sample)]×100.

[0554] Maximum and spontaneous release are determined by incubating thelabeled targets with 1% Triton X-100 and media alone, respectively. Apositive culture is defined as one in which the specific lysis(sample-background) is 10% or higher in the case of individual wells andis 15% or more at the two highest E:T ratios when expanded cultures areassayed.

[0555] In situ Measurement of Human IFNγ Production as an Indicator ofPeptide-Specific and Endogenous Recognition

[0556] Immulon 2 plates are coated with mouse anti-human IFNγ monoclonalantibody (4 μg/ml 0.1M NaHCO₃, pH8.2) overnight at 4° C. The plates arewashed with Ca²⁺, Mg²⁺-free PBS/0.05% Tween 20 and blocked with PBS/10%FCS for two hours, after which the CTLs (100 μl/well) and targets (100μl/well) are added to each well, leaving empty wells for the standardsand blanks (which received media only). The target cells, eitherpeptide-pulsed or endogenous targets, are used at a concentration of1×10⁶ cells/ml. The plates are incubated for 48 hours at 37° C. with 5%CO₂.

[0557] Recombinant human IFN-gamma is added to the standard wellsstarting at 400 pg or 120 pg/100 microliter/well and the plate incubatedfor two hours at 37° C. The plates are washed and 100 μl of biotinylatedmouse anti-human IFN-gamma monoclonal antibody (2 microgram/ml in PBS/3%FCS/0.05% Tween 20) are added and incubated for 2 hours at roomtemperature. After washing again, 100 microliter HRP-streptavidin(1:4000) are added and the plates incubated for one hour at roomtemperature. The plates are then washed 6× with wash buffer, 100microliter/well developing solution (TMB 1:1) are added, and the platesallowed to develop for 5-15 minutes. The reaction is stopped with 50microliter/well 1M H₃PO₄ and read at OD450. A culture is consideredpositive if it measured at least 50 pg of IFN-gamma/well abovebackground and is twice the background level of expression.

[0558] CTL Expansion.

[0559] Those cultures that demonstrate specific lytic activity againstpeptide-pulsed targets and/or tumor targets are expanded over a two weekperiod with anti-CD3. Briefly, 5×10⁴ CD8+ cells are added to a T25 flaskcontaining the following: 1×10⁶ irradiated (4,200 rad) PBMC (autologousor allogeneic) per ml, 2×10⁵ irradiated (8,000 rad) EBV-transformedcells per ml, and OKT3 (anti-CD3) at 30 ng per ml in RPMI-1640containing 10% (v/v) human AB serum, non-essential amino acids, sodiumpyruvate, 25 μM 2-mercaptoethanol, L-glutamine andpenicillin/streptomycin. Recombinant human IL2 is added 24 hours laterat a final concentration of 200 IU/ml and every three days thereafterwith fresh media at 50 IU/ml. The cells are split if the cellconcentration exceeds 1×10⁶/ml and the cultures are assayed between days13 and 15 at E:T ratios of 30, 10, 3 and 1:1 in the ⁵¹Cr release assayor at 1×10⁶/ml in the in situ IFNγ assay using the same targets asbefore the expansion.

[0560] Cultures are expanded in the absence of anti-CD3⁺ as follows.Those cultures that demonstrate specific lytic activity against peptideand endogenous targets are selected and 5×10⁴ CD8⁺ cells are added to aT25 flask containing the following: 1×10⁶ autologous PBMC per ml whichhave been peptide-pulsed with 10 μg/ml peptide for two hours at 37° C.and irradiated (4,200 rad); 2×10⁵ irradiated (8,000 rad) EBV-transformedcells per ml RPMI-1640 containing 10% (v/v) human AB serum,non-essential AA, sodium pyruvate, 25 mM 2-ME, L-glutamine andgentamicin.

[0561] Immunogenicity of A2 Supermotif-Bearing Peptides

[0562] A2-supermotif cross-reactive binding peptides are tested in thecellular assay for the ability to induce peptide-specific CTL in normalindividuals. In this analysis, a peptide is typically considered to bean epitope if it induces peptide-specific CTLs in at least individuals,and preferably, also recognizes the endogenously expressed peptide.

[0563] Immunogenicity can also be confirmed using PBMCs isolated frompatients bearing a tumor that expresses 151P3D4. Briefly, PBMCs areisolated from patients, re-stimulated with peptide-pulsed monocytes andassayed for the ability to recognize peptide-pulsed target cells as wellas transfected cells endogenously expressing the antigen.

[0564] Evaluation of A*03/A11 Immunogenicity

[0565] HLA-A3 supermotif-bearing cross-reactive binding peptides arealso evaluated for immunogenicity using methodology analogous for thatused to evaluate the immunogenicity of the HLA-A2 supermotif peptides.

[0566] Evaluation of B7 Immunogenicity

[0567] Immunogenicity screening of the B7-supertype cross-reactivebinding peptides identified as set forth herein are confirmed in amanner analogous to the confirmation of A2-and A3-supermotif-bearingpeptides.

[0568] Peptides bearing other supermotifs/motifs, e.g., HLA-A1, HLA-A24etc. are also confirmed using similar methodology

Example 15

[0569] Implementation of the Extended Supermotif to Improve the BindingCapacity of Native Epitopes by Creating Analogs

[0570] HLA motifs and supermotifs (comprising primary and/or secondaryresidues) are useful in the identification and preparation of highlycross-reactive native peptides, as demonstrated herein. Moreover, thedefinition of HLA motifs and supermotifs also allows one to engineerhighly cross-reactive epitopes by identifying residues within a nativepeptide sequence which can be analoged to confer upon the peptidecertain characteristics, e.g. greater cross-reactivity within the groupof HLA molecules that comprise a supertype, and/or greater bindingaffinity for some or all of those HLA molecules. Examples of analogingpeptides to exhibit modulated binding affinity are set forth in thisexample.

[0571] Analoging at Primary Anchor Residues

[0572] Peptide engineering strategies are implemented to furtherincrease the cross-reactivity of the epitopes. For example, the mainanchors of A2-supermotif-bearing peptides are altered, for example, tointroduce a preferred L, I, V, or M at position 2, and I or V at theC-terminus.

[0573] To analyze the cross-reactivity of the analog peptides, eachengineered analog is initially tested for binding to the prototype A2supertype allele A*0201, then, if A*0201 binding capacity is maintained,for A2-supertype cross-reactivity.

[0574] Alternatively, a peptide is confirmed as binding one or allsupertype members and then analoged to modulate binding affinity to anyone (or more) of the supertype members to add population coverage.

[0575] The selection of analogs for immunogenicity in a cellularscreening analysis is typically further restricted by the capacity ofthe parent wild type (WT) peptide to bind at least weakly, i.e., bind atan IC₅₀ of 5000 nM or less, to three of more A2 supertype alleles. Therationale for this requirement is that the WT peptides must be presentendogenously in sufficient quantity to be biologically relevant.Analoged peptides have been shown to have increased immunogenicity andcross-reactivity by T cells specific for the parent epitope (see, e.g.,Parkhurst et al., J. Immunol. 157:2539, 1996; and Pogue et al., Proc.Natl. Acad. Sci. USA 92:8166, 1995).

[0576] In the cellular screening of these peptide analogs, it isimportant to confirm that analog-specific CTLs are also able torecognize the wild-type peptide and, when possible, target cells thatendogenously express the epitope.

[0577] Analoging of HLA-A3 and B7-Supermotif-Bearing Peptides

[0578] Analogs of HLA-A3 supermotif-bearing epitopes are generated usingstrategies similar to those employed in analoging HLA-A2supermotif-bearing peptides. For example, peptides binding to 3/5 of theA3-supertype molecules are engineered at primary anchor residues topossess a preferred residue (V, S, M, or A) at position 2.

[0579] The analog peptides are then tested for the ability to bind A*03and A*11 (prototype A3 supertype alleles). Those peptides thatdemonstrate ≦500 nM binding capacity are then confirmed as havingA3-supertype cross-reactivity.

[0580] Similarly to the A2- and A3-motif bearing peptides, peptidesbinding 3 or more B7-supertype alleles can be improved, where possible,to achieve increased cross-reactive binding or greater binding affinityor binding half life. B7 supermotif-bearing peptides are, for example,engineered to possess a preferred residue (V, I, L, or F) at theC-terminal primary anchor position, as demonstrated by Sidney et al. (J.Immunol. 157:3480-3490, 1996).

[0581] Analoging at primary anchor residues of other motif and/orsupermotif-bearing epitopes is performed in a like manner.

[0582] The analog peptides are then be confirmed for immunogenicity,typically in a cellular screening assay. Again, it is generallyimportant to demonstrate that analog-specific CTLs are also able torecognize the wild-type peptide and, when possible, targets thatendogenously express the epitope.

[0583] Analoging at Secondary Anchor Residues

[0584] Moreover, HLA supermotifs are of value in engineering highlycross-reactive peptides and/or peptides that bind HLA molecules withincreased affinity by identifying particular residues at secondaryanchor positions that are associated with such properties. For example,the binding capacity of a B7 supermotif-bearing peptide with an Fresidue at position 1 is analyzed. The peptide is then analoged to, forexample, substitute L for F at position 1. The analoged peptide isevaluated for increased binding affinity, binding half life and/orincreased cross-reactivity. Such a procedure identifies analogedpeptides with enhanced properties.

[0585] Engineered analogs with sufficiently improved binding capacity orcross-reactivity can also be tested for immunogenicity inHLA-B7-transgenic mice, following for example, IFA immunization orlipopeptide immunization. Analoged peptides are additionally tested forthe ability to stimulate a recall response using PBMC from patients with151P3D4-expressing tumors.

[0586] Other Analoging Strategies

[0587] Another form of peptide analoging, unrelated to anchor positions,involves the substitution of a cysteine with α-amino butyric acid. Dueto its chemical nature, cysteine has the propensity to form disulfidebridges and sufficiently alter the peptide structurally so as to reducebinding capacity. Substitution of α-amino butyric acid for cysteine notonly alleviates this problem, but has been shown to improve binding andcrossbinding capabilities in some instances (see, e.g., the review bySette et al., In: Persistent Viral Infections, Eds. R. Ahmed and I.Chen, John Wiley & Sons, England, 1999).

[0588] Thus, by the use of single amino acid substitutions, the bindingproperties and/or cross-reactivity of peptide ligands for HLA supertypemolecules can be modulated.

Example 16

[0589] Identification and Confirmation of 151P3D4-derived Sequences withHLA-DR Binding Motifs

[0590] Peptide epitopes bearing an HLA class II supermotif or motif areidentified and confirmed as outlined below using methodology similar tothat described for HLA Class I peptides.

[0591] Selection of HLA-DR-Supermotif-Bearing Epitopes.

[0592] To identify 151P3D4-derived, HLA class II HTL epitopes, a 151P3D4antigen is analyzed for the presence of sequences bearing anHLA-DR-motif or supermotif. Specifically, 15-mer sequences are selectedcomprising a DR-supermotif, comprising a 9-mer core, and three-residueN- and C-terminal flanking regions (15 amino acids total).

[0593] Protocols for predicting peptide binding to DR molecules havebeen developed (Southwood et al., J. Immunol. 160:3363-3373, 1998).These protocols, specific for individual DR molecules, allow thescoring, and ranking, of 9-mer core regions. Each protocol not onlyscores peptide sequences for the presence of DR-supermotif primaryanchors (i.e., at position 1 and position 6) within a 9-mer core, butadditionally evaluates sequences for the presence of secondary anchors.Using allele-specific selection tables (see, e.g., Southwood et al.,ibid.), it has been found that these protocols efficiently selectpeptide sequences with a high probability of binding a particular DRmolecule. Additionally, it has been found that performing theseprotocols in tandem, specifically those for DR1, DR4w4, and DR7, canefficiently select DR cross-reactive peptides.

[0594] The 151P3D4-derived peptides identified above are tested fortheir binding capacity for various common HLA-DR molecules. All peptidesare initially tested for binding to the DR molecules in the primarypanel: DR1, DR4w4, and DR7. Peptides binding at least two of these threeDR molecules are then tested for binding to DR2w2 β1, DR2w2 β2, DR6w19,and DR9 molecules in secondary assays. Finally, peptides binding atleast two of the four secondary panel DR molecules, and thuscumulatively at least four of seven different DR molecules, are screenedfor binding to DR4w15, DR5w11, and DR8w2 molecules in tertiary assays.Peptides binding at least seven of the ten DR molecules comprising theprimary, secondary, and tertiary screening assays are consideredcross-reactive DR binders. 151P3D4-derived peptides found to bind commonHLA-DR alleles are of particular interest.

[0595] Selection of DR3 Motif Peptides

[0596] Because HLA-DR3 is an allele that is prevalent in Caucasian,Black, and Hispanic populations, DR3 binding capacity is a relevantcriterion in the selection of HTL epitopes. Thus, peptides shown to becandidates may also be assayed for their DR3 binding capacity. However,in view of the binding specificity of the DR3 motif, peptides bindingonly to DR3 can also be considered as candidates for inclusion in avaccine formulation.

[0597] To efficiently identify peptides that bind DR3, target 151P3D4antigens are analyzed for sequences carrying one of the two DR3-specificbinding motifs reported by Geluk et al. (J. Immunol. 152:5742-5748,1994). The corresponding peptides are then synthesized and confirmed ashaving the ability to bind DR3 with an affinity of 1 μM or better, i.e.,less than 1 μM. Peptides are found that meet this binding criterion andqualify as HLA class II high affinity binders.

[0598] DR3 binding epitopes identified in this manner are included invaccine compositions with DR supermotif-bearing peptide epitopes.

[0599] Similarly to the case of HLA class I motif-bearing peptides, theclass II motif-bearing peptides are analoged to improve affinity orcross-reactivity. For example, aspartic acid at position 4 of the 9-mercore sequence is an optimal residue for DR3 binding, and substitutionfor that residue often improves DR 3 binding.

Example 17

[0600] Immunogenicity of 151P3D4-Derived HTL Epitopes

[0601] This example determines immunogenic DR supermotif- and DR3motif-bearing epitopes among those identified using the methodology setforth herein.

[0602] Immunogenicity of HTL epitopes are confirmed in a manneranalogous to the determination of immunogenicity of CTL epitopes, byassessing the ability to stimulate HTL responses and/or by usingappropriate transgenic mouse models. Immunogenicity is determined byscreening for: 1.) in vitro primary induction using normal PBMC or 2.)recall responses from patients who have 151P3D4-expressing tumors.

Example 18

[0603] Calculation of Phenotypic Frequencies of HLA-Supertypes inVarious Ethnic Backgrounds to Determine Breadth of Population Coverage

[0604] This example illustrates the assessment of the breadth ofpopulation coverage of a vaccine composition comprised of multipleepitopes comprising multiple supermotifs and/or motifs.

[0605] In order to analyze population coverage, gene frequencies of HLAalleles are determined. Gene frequencies for each HLA allele arecalculated from antigen or allele frequencies utilizing the binomialdistribution formulae gf=1-(SQRT(1-af)) (see, e.g., Sidney et al., HumanImmunol. 45:79-93, 1996). To obtain overall phenotypic frequencies,cumulative gene frequencies are calculated, and the cumulative antigenfrequencies derived by the use of the inverse formula [af=1-(1-Cgf)²].

[0606] Where frequency data is not available at the level of DNA typing,correspondence to the serologically defined antigen frequencies isassumed. To obtain total potential supertype population coverage nolinkage disequilibrium is assumed, and only alleles confirmed to belongto each of the supertypes are included (minimal estimates). Estimates oftotal potential coverage achieved by inter-loci combinations are made byadding to the A coverage the proportion of the non-A covered populationthat could be expected to be covered by the B alleles considered (e.g.,total=A+B*(1−A)). Confirmed members of the A3-like supertype are A3,A11, A31, A*3301, and A*6801. Although the A3-like supertype may alsoinclude A34, A66, and A*7401, these alleles were not included in overallfrequency calculations. Likewise, confirmed members of the A2-likesupertype family are A*0201, A*0202, A*0203, A*0204, A*0205, A*0206,A*0207, A*6802, and A*6901. Finally, the B7-like supertype-confirmedalleles are: B7, B*3501-03, B51, B*5301, B*5401, B*5501-2, B*5601,B*6701, and B*7801 (potentially also B*1401, B*3504-06, B*4201, andB*5602).

[0607] Population coverage achieved by combining the A2-, A3- andB7-supertypes is approximately 86% in five major ethnic groups. Coveragemay be extended by including peptides bearing the A1 and A24 motifs. Onaverage, A1 is present in 12% and A24 in 29% of the population acrossfive different major ethnic groups (Caucasian, North American Black,Chinese, Japanese, and Hispanic). Together, these alleles arerepresented with an average frequency of 39% in these same ethnicpopulations. The total coverage across the major ethnicities when A1 andA24 are combined with the coverage of the A2-, A3- and B7-supertypealleles is >95%. An analogous approach can be used to estimatepopulation coverage achieved with combinations of class II motif-bearingepitopes.

[0608] Immunogenicity studies in humans (e.g., Bertoni et al., J. Clin.Invest. 100:503, 1997; Doolan et al., Immunity 7:97, 1997; and Threlkeldet al., J. Immunol. 159:1648, 1997) have shown that highlycross-reactive binding peptides are almost always recognized asepitopes. The use of highly cross-reactive binding peptides is animportant selection criterion in identifying candidate epitopes forinclusion in a vaccine that is immunogenic in a diverse population.

[0609] With a sufficient number of epitopes (as disclosed herein andfrom the art), an average population coverage is predicted to be greaterthan 95% in each of five major ethnic populations. The game theory MonteCarlo simulation analysis, which is known in the art (see e.g., Osborne,M. J. and Rubinstein, A. “A course in game theory” MIT Press, 1994), canbe used to estimate what percentage of the individuals in a populationcomprised of the Caucasian, North American Black, Japanese, Chinese, andHispanic ethnic groups would recognize the vaccine epitopes describedherein. A preferred percentage is 90%. A more preferred percentage is95%.

Example 19

[0610] CTL Recognition of Endogenously Processed Antigens after Priming

[0611] This example confirms that CTL induced by native or analogedpeptide epitopes identified and selected as described herein recognizeendogenously synthesized, i.e., native antigens.

[0612] Effector cells isolated from transgenic mice that are immunizedwith peptide epitopes, for example HLA-A2 supermotif-bearing epitopes,are re-stimulated in vitro using peptide-coated stimulator cells. Sixdays later, effector cells are assayed for cytotoxicity and the celllines that contain peptide-specific cytotoxic activity are furtherre-stimulated. An additional six days later, these cell lines are testedfor cytotoxic activity on ⁵¹Cr labeled Jurkat-A2.1/K^(b) target cells inthe absence or presence of peptide, and also tested on ⁵¹Cr labeledtarget cells bearing the endogenously synthesized antigen, i.e. cellsthat are stably transfected with 151P3D4 expression vectors.

[0613] The results demonstrate that CTL lines obtained from animalsprimed with peptide epitope recognize endogenously synthesized 151P3D4antigen. The choice of transgenic mouse model to be used for such ananalysis depends upon the epitope(s) that are being evaluated. Inaddition to HLA-A*0201/K^(b) transgenic mice, several other transgenicmouse models including mice with human A11, which may also be used toevaluate A3 epitopes, and B7 alleles have been characterized and others(e.g., transgenic mice for HLA-A1 and A24) are being developed. HLA-DR1and HLA-DR3 mouse models have also been developed, which may be used toevaluate HTL epitopes.

Example 20

[0614] Activity of CTL-HTL Conjugated Epitopes in Transgenic Mice

[0615] This example illustrates the induction of CTLs and HTLs intransgenic mice, by use of a 151P3D4-derived CTL and HTL peptide vaccinecompositions. The vaccine composition used herein comprise peptides tobe administered to a patient with a 151P3D4-expressing tumor. Thepeptide composition can comprise multiple CTL and/or HTL epitopes. Theepitopes are identified using methodology as described herein. Thisexample also illustrates that enhanced immunogenicity can be achieved byinclusion of one or more HTL epitopes in a CTL vaccine composition; sucha peptide composition can comprise an HTL epitope conjugated to a CTLepitope. The CTL epitope can be one that binds to multiple HLA familymembers at an affinity of 500 nM or less, or analogs of that epitope.The peptides may be lipidated, if desired.

[0616] Immunization procedures: Immunization of transgenic mice isperformed as described (Alexander et al., J. Immunol. 159:4753-4761,1997). For example, A2/K^(b) mice, which are transgenic for the humanHLA A2.1 allele and are used to confirm the immunogenicity of HLA-A*0201motif- or HLA-A2 supermotif-bearing epitopes, and are primedsubcutaneously (base of the tail) with a 0.1 ml of peptide in IncompleteFreund's Adjuvant, or if the peptide composition is a lipidated CTL/HTLconjugate, in DMSO/saline, or if the peptide composition is apolypeptide, in PBS or Incomplete Freund's Adjuvant. Seven days afterpriming, splenocytes obtained from these animals are restimulated withsyngenic irradiated LPS-activated lymphoblasts coated with peptide.

[0617] Cell lines: Target cells for peptide-specific cytotoxicity assaysare Jurkat cells transfected with the HLA-A2.1/K^(b) chimeric gene(e.g., Vitiello et al., J. Exp. Med. 173:1007, 1991)

[0618] In vitro CTL activation: One week after priming, spleen cells(30×10⁶ cells/flask) are co-cultured at 37° C. with syngeneic,irradiated (3000 rads), peptide coated lymphoblasts (10×10⁶ cells/flask)in 10 ml of culture medium/T25 flask. After six days, effector cells areharvested and assayed for cytotoxic activity.

[0619] Assay for cytotoxic activity: Target cells (1.0 to 1.5×10⁶) areincubated at 37° C. in the presence of 200 μl of ⁵¹Cr. After 60 minutes,cells are washed three times and resuspended in R10 medium. Peptide isadded where required at a concentration of 1 μg/ml. For the assay, 10⁴⁵¹Cr-labeled target cells are added to different concentrations ofeffector cells (final volume of 200 μl) in U-bottom 96-well plates.After a six hour incubation period at 37° C., a 0.1 ml aliquot ofsupernatant is removed from each well and radioactivity is determined ina Micromedic automatic gamma counter. The percent specific lysis isdetermined by the formula: percent specific release=100×(experimentalrelease−spontaneous release)/(maximum release−spontaneous release). Tofacilitate comparison between separate CTL assays run under the sameconditions, % ⁵¹Cr release data is expressed as lytic units/10⁶ cells.One lytic unit is arbitrarily defined as the number of effector cellsrequired to achieve 30% lysis of 10,000 target cells in a six hour ⁵¹Crrelease assay. To obtain specific lytic units/10⁶, the lytic units/10⁶obtained in the absence of peptide is subtracted from the lyticunits/10⁶ obtained in the presence of peptide. For example, if 30% ⁵¹Crrelease is obtained at the effector (E): target (T) ratio of 50:1 (i.e.,5×10⁵ effector cells for 10,000 targets) in the absence of peptide and5:1 (i.e., 5×10⁴ effector cells for 10,000 targets) in the presence ofpeptide, the specific lytic units would be: [(1/50,000)−(1/500,000)]×10⁶=18 LU.

[0620] The results are analyzed to assess the magnitude of the CTLresponses of animals injected with the immunogenic CTL/HTL conjugatevaccine preparation and are compared to the magnitude of the CTLresponse achieved using, for example, CTL epitopes as outlined above inthe Example entitled “Confirmation of Immunogenicity.” Analyses similarto this may be performed to confirm the immunogenicity of peptideconjugates containing multiple CTL epitopes and/or multiple HTLepitopes. In accordance with these procedures, it is found that a CTLresponse is induced, and concomitantly that an HTL response is inducedupon administration of such compositions.

Example 21

[0621] Selection of CTL and HTL Epitopes for Inclusion in a151P3D4-Specific Vaccine.

[0622] This example illustrates a procedure for selecting peptideepitopes for vaccine compositions of the invention. The peptides in thecomposition can be in the form of a nucleic acid sequence, either singleor one or more sequences (i.e., minigene) that encodes peptide(s), orcan be single and/or polyepitopic peptides.

[0623] The following principles are utilized when selecting a pluralityof epitopes for inclusion in a vaccine composition. Each of thefollowing principles is balanced in order to make the selection.

[0624] Epitopes are selected which, upon administration, mimic immuneresponses that are correlated with 151P3D4 clearance. The number ofepitopes used depends on observations of patients who spontaneouslyclear 151P3D4. For example, if it has been observed that patients whospontaneously clear 151P3D4-expressing cells generate an immune responseto at least three (3) epitopes from 151P3D4 antigen, then at least threeepitopes should be included for HLA class I. A similar rationale is usedto determine HLA class II epitopes.

[0625] Epitopes are often selected that have a binding affinity of anIC₅₀ of 500 nM or less for an HLA class I molecule, or for class II, anIC₅₀ of 1000 nM or less; or HLA Class I peptides with high bindingscores from the BIMAS web site, at URL bimas.dcrt.nih.gov/.

[0626] In order to achieve broad coverage of the vaccine through out adiverse population, sufficient supermotif bearing peptides, or asufficient array of allele-specific motif bearing peptides, are selectedto give broad population coverage. In one embodiment, epitopes areselected to provide at least 80% population coverage. A Monte Carloanalysis, a statistical evaluation known in the art, can be employed toassess breadth, or redundancy, of population coverage.

[0627] When creating polyepitopic compositions, or a minigene thatencodes same, it is typically desirable to generate the smallest peptidepossible that encompasses the epitopes of interest. The principlesemployed are similar, if not the same, as those employed when selectinga peptide comprising nested epitopes. For example, a protein sequencefor the vaccine composition is selected because it has maximal number ofepitopes contained within the sequence, i.e., it has a highconcentration of epitopes. Epitopes may be nested or overlapping (i.e.,frame shifted relative to one another). For example, with overlappingepitopes, two 9-mer epitopes and one 10-mer epitope can be present in a10 amino acid peptide. Each epitope can be exposed and bound by an HLAmolecule upon administration of such a peptide. A multi-epitopic,peptide can be generated synthetically, recombinantly, or via cleavagefrom the native source. Alternatively, an analog can be made of thisnative sequence, whereby one or more of the epitopes comprisesubstitutions that alter the cross-reactivity and/or binding affinityproperties of the polyepitopic peptide. Such a vaccine composition isadministered for therapeutic or prophylactic purposes. This embodimentprovides for the possibility that an as yet undiscovered aspect ofimmune system processing will apply to the native nested sequence andthereby facilitate the production of therapeutic or prophylactic immuneresponse-inducing vaccine compositions. Additionally such an embodimentprovides for the possibility of motif-bearing epitopes for an HLA makeupthat is presently unknown. Furthermore, this embodiment (absent thecreating of any analogs) directs the immune response to multiple peptidesequences that are actually present in 151P3D4, thus avoiding the needto evaluate any junctional epitopes. Lastly, the embodiment provides aneconomy of scale when producing nucleic acid vaccine compositions.Related to this embodiment, computer programs can be derived inaccordance with principles in the art, which identify in a targetsequence, the greatest number of epitopes per sequence length.

[0628] A vaccine composition comprised of selected peptides, whenadministered, is safe, efficacious, and elicits an immune responsesimilar in magnitude to an immune response that controls or clears cellsthat bear or overexpress 151P3D4.

Example 22

[0629] Construction of “Minigene” Multi-Enitope DNA Plasmids

[0630] This example discusses the construction of a minigene expressionplasmid. Minigene plasmids may, of course, contain variousconfigurations of B cell, CTL and/or HTL epitopes or epitope analogs asdescribed herein.

[0631] A minigene expression plasmid typically includes multiple CTL andHTL peptide epitopes. In the present example, HLA-A2, -A3, -B7supermotif-bearing peptide epitopes and HLA-A1 and -A24 motif-bearingpeptide epitopes are used in conjunction with DR supermotif-bearingepitopes and/or DR3 epitopes. HLA class I supermotif or motif-bearingpeptide epitopes derived 151P3D4, are selected such that multiplesupermotifs/motifs are represented to ensure broad population coverage.Similarly, HLA class II epitopes are selected from 151P3D4 to providebroad population coverage, i.e. both HLA DR-1-4-7 supermotif-bearingepitopes and HLA DR-3 motif-bearing epitopes are selected for inclusionin the minigene construct. The selected CTL and HTL epitopes are thenincorporated into a minigene for expression in an expression vector.

[0632] Such a construct may additionally include sequences that directthe HTL epitopes to the endoplasmic reticulum. For example, the Iiprotein may be fused to one or more HTL epitopes as described in theart, wherein the CLIP sequence of the Ii protein is removed and replacedwith an HLA class II epitope sequence so that HLA class II epitope isdirected to the endoplasmic reticulum, where the epitope binds to an HLAclass II molecules.

[0633] This example illustrates the methods to be used for constructionof a minigene-bearing expression plasmid. Other expression vectors thatmay be used for ninigene compositions are available and known to thoseof skill in the art.

[0634] The minigene DNA plasmid of this example contains a consensusKozak sequence and a consensus murine kappa Ig-light chain signalsequence followed by CTL and/or HTL epitopes selected in accordance withprinciples disclosed herein. The sequence encodes an open reading framefused to the Myc and His antibody epitope tag coded for by the pcDNA 3.1Myc-His vector.

[0635] Overlapping oligonucleotides that can, for example, average about70 nucleotides in length with 15 nucleotide overlaps, are synthesizedand HPLC-purified. The oligonucleotides encode the selected peptideepitopes as well as appropriate linker nucleotides, Kozak sequence, andsignal sequence. The final multiepitope minigene is assembled byextending the overlapping oligonucleotides in three sets of reactionsusing PCR. A Perkin/Elmer 9600 PCR machine is used and a total of 30cycles are performed using the following conditions: 95° C. for 15 sec,annealing temperature (5° below the lowest calculated Tm of each primerpair) for 30 sec, and 72° C. for 1 min.

[0636] For example, a minigene is prepared as follows. For a first PCRreaction, 5 μg of each of two oligonucleotides are annealed andextended: In an example using eight oligonucleotides, i.e., four pairsof primers, oligonucleotides 1+2, 3+4, 5+6, and 7+8 are combined in 100μl reactions contain Pfu polymerase buffer (1×=10 mM KCL, 10 mM(NH4)₂SO₄, 20 mM Tris-chloride, pH 8.75, 2 mM MgSO₄, 0.1% Triton X-100,100 μg/ml BSA), 0.25 mM each dNTP, and 2.5 U of Pfu polymerase. Thefull-length dimer products are gel-purified, and two reactionscontaining the product of 1+2 and 3+4, and the product of 5+6 and 7+8are mixed, annealed, and extended for 10 cycles. Half of the tworeactions are then mixed, and cycles of annealing and extension carriedout before flanking primers are added to amplify the full lengthproduct. The full-length product is gel-purified and cloned intopCR-blunt (Invitrogen) and individual clones are screened by sequencing.

Example 23

[0637] The Plasmid Construct and the Degree to Which It InducesImmunogenicity.

[0638] The degree to which a plasmid construct, for example a plasmidconstructed in accordance with the previous Example, is able to induceimmunogenicity is confirmed in vitro by determining epitope presentationby APC following transduction or transfection of the APC with anepitope-expressing nucleic acid construct. Such a study determines“antigenicity” and allows the use of human APC. The assay determines theability of the epitope to be presented by the APC in a context that isrecognized by a T cell by quantifying the density of epitope-HLA class Icomplexes on the cell surface. Quantitation can be performed by directlymeasuring the amount of peptide eluted from the APC (see, e.g., Sijts etal., J. Immunol. 156:683-692, 1996; Demotz et al., Nature 342:682-684,1989); or the number of peptide-HLA class I complexes can be estimatedby measuring the amount of lysis or lymphokine release induced bydiseased or transfected target cells, and then determining theconcentration of peptide necessary to obtain equivalent levels of lysisor lymphokine release (see, e.g., Kageyama et al., J. Immunol.154:567-576, 1995).

[0639] Alternatively, immunogenicity is confirmed through in vivoinjections into mice and subsequent in vitro assessment of CTL and HTLactivity, which are analyzed using cytotoxicity and proliferationassays, respectively, as detailed e.g., in Alexander et al., Immunity1:751-761, 1994.

[0640] For example, to confirm the capacity of a DNA minigene constructcontaining at least one HLA-A2 supermotif peptide to induce CTLs invivo, HLA-A2.1/K^(b) transgenic mice, for example, are immunizedintramuscularly with 100 μg of naked cDNA. As a means of comparing thelevel of CTLs induced by cDNA immunization, a control group of animalsis also immunized with an actual peptide composition that comprisesmultiple epitopes synthesized as a single polypeptide as they would beencoded by the minigene.

[0641] Splenocytes from immunized animals are stimulated twice with eachof the respective compositions (peptide epitopes encoded in the minigeneor the polyepitopic peptide), then assayed for peptide-specificcytotoxic activity in a ⁵¹Cr release assay. The results indicate themagnitude of the CTL response directed against the A2-restrictedepitope, thus indicating the in vivo immunogenicity of the minigenevaccine and polyepitopic vaccine.

[0642] It is, therefore, found that the minigene elicits immuneresponses directed toward the HLA-A2 supermotif peptide epitopes as doesthe polyepitopic peptide vaccine. A similar analysis is also performedusing other HLA-A3 and HLA-B7 transgenic mouse models to assess CTLinduction by HLA-A3 and HLA-B7 motif or supermotif epitopes, whereby itis also found that the minigene elicits appropriate immune responsesdirected toward the provided epitopes.

[0643] To confirm the capacity of a class II epitope-encoding minigeneto induce HTLs in vivo, DR transgenic mice, or for those epitopes thatcross react with the appropriate mouse MHC molecule, I-A^(b)-restrictedmice, for example, are immunized intramuscularly with 100 μg of plasmidDNA. As a means of comparing the level of HTLs induced by DNAimmunization, a group of control animals is also immunized with anactual peptide composition emulsified in complete Freund's adjuvant.CD4+ T cells, i.e. HTLs, are purified from splenocytes of immunizedanimals and stimulated with each of the respective compositions(peptides encoded in the minigene). The HTL response is measured using a³H-thymidine incorporation proliferation assay, (see, e.g., Alexander etal. Immunity 1:751-761, 1994). The results indicate the magnitude of theHTL response, thus demonstrating the in vivo immunogenicity of theminigene.

[0644] DNA minigenes, constructed as described in the previous Example,can also be confirmed as a vaccine in combination with a boosting agentusing a prime boost protocol. The boosting agent can consist ofrecombinant protein (e.g., Barnett et al., Aids Res. and HumanRetroviruses 14, Supplement 3:S299-S309, 1998) or recombinant vaccinia,for example, expressing a minigene or DNA encoding the complete proteinof interest (see, e.g., Hanke et al., Vaccine 16:439-445, 1998; Sedegahet al., Proc. Natl. Acad. Sci USA 95:7648-53, 1998; Hanke and McMichael,Immunol. Letters 66:177-181, 1999; and Robinson et al., Nature Med.5:526-34, 1999).

[0645] For example, the efficacy of the DNA minigene used in a primeboost protocol is initially evaluated in transgenic mice. In thisexample, A2.1/K^(b) transgenic mice are immunized IM with 100 μg of aDNA minigene encoding the immunogenic peptides including at least oneHLA-A2 supermotif-bearing peptide. After an incubation period (rangingfrom 3-9 weeks), the mice are boosted IP with 10⁷ pfu/mouse of arecombinant vaccinia virus expressing the same sequence encoded by theDNA minigene. Control mice are immunized with 100 μg of DNA orrecombinant vaccinia without the minigene sequence, or with DNA encodingthe minigene, but without the vaccinia boost. After an additionalincubation period of two weeks, splenocytes from the mice areimmediately assayed for peptide-specific activity in an ELISPOT assay.Additionally, splenocytes are stimulated in vitro with the A2-restrictedpeptide epitopes encoded in the minigene and recombinant vaccinia, thenassayed for peptide-specific activity in an alpha, beta and/or gamma IFNELISA.

[0646] It is found that the minigene utilized in a prime-boost protocolelicits greater immune responses toward the HLA-A2 supermotif peptidesthan with DNA alone. Such an analysis can also be performed usingHLA-A11 or HLA-B7 transgenic mouse models to assess CTL induction byHLA-A3 or HLA-B7 motif or supermotif epitopes. The use of prime boostprotocols in humans is described below in the Example entitled“Induction of CTL Responses Using a Prime Boost Protocol.”

Example 24

[0647] Peptide Compositions for Prophylactic Uses

[0648] Vaccine compositions of the present invention can be used toprevent 151P3D4 expression in persons who are at risk for tumors thatbear this antigen. For example, a polyepitopic peptide epitopecomposition (or a nucleic acid comprising the same) containing multipleCTL and HTL epitopes such as those selected in the above Examples, whichare also selected to target greater than 80% of the population, isadministered to individuals at risk for a 151P3D4-associated tumor.

[0649] For example, a peptide-based composition is provided as a singlepolypeptide that encompasses multiple epitopes. The vaccine is typicallyadministered in a physiological solution that comprises an adjuvant,such as Incomplete Freunds Adjuvant. The dose of peptide for the initialimmunization is from about 1 to about 50,000 μg, generally 100-5,000 μg,for a 70 kg patient. The initial administration of vaccine is followedby booster dosages at 4 weeks followed by evaluation of the magnitude ofthe immune response in the patient, by techniques that determine thepresence of epitope-specific CTL populations in a PBMC sample.Additional booster doses are administered as required. The compositionis found to be both safe and efficacious as a prophylaxis against151P3D4-associated disease.

[0650] Alternatively, a composition typically comprising transfectingagents is used for the administration of a nucleic acid-based vaccine inaccordance with methodologies known in the art and disclosed herein.

Example 25

[0651] Polyepitopic Vaccine Compositions Derived from Native 151P3D4Sequences

[0652] A native 151P3D4 polyprotein sequence is analyzed, preferablyusing computer algorithms defined for each class I and/or class IIsupermotif or motif, to identify “relatively short” regions of thepolyprotein that comprise multiple epitopes. The “relatively short”regions are preferably less in length than an entire native antigen.This relatively short sequence that contains multiple distinct oroverlapping, “nested” epitopes can be used to generate a minigeneconstruct. The construct is engineered to express the peptide, whichcorresponds to the native protein sequence. The “relatively short”peptide is generally less than 250 amino acids in length, often lessthan 100 amino acids in length, preferably less than 75 amino acids inlength, and more preferably less than 50 amino acids in length. Theprotein sequence of the vaccine composition is selected because it hasmaximal number of epitopes contained within the sequence, i.e., it has ahigh concentration of epitopes. As noted herein, epitope motifs may benested or overlapping (i.e., frame shifted relative to one another). Forexample, with overlapping epitopes, two 9-mer epitopes and one 10-merepitope can be present in a 10 amino acid peptide. Such a vaccinecomposition is administered for therapeutic or prophylactic purposes.

[0653] The vaccine composition will include, for example, multiple CTLepitopes from 151P3D4 antigen and at least one HTL epitope. Thispolyepitopic native sequence is administered either as a peptide or as anucleic acid sequence which encodes the peptide. Alternatively, ananalog can be made of this native sequence, whereby one or more of theepitopes comprise substitutions that alter the cross-reactivity and/orbinding affinity properties of the polyepitopic peptide.

[0654] The embodiment of this example provides for the possibility thatan as yet undiscovered aspect of immune system processing will apply tothe native nested sequence and thereby facilitate the production oftherapeutic or prophylactic immune response-inducing vaccinecompositions. Additionally, such an embodiment provides for thepossibility of motif-bearing epitopes for an HLA makeup(s) that ispresently unknown. Furthermore, this embodiment (excluding an analogedembodiment) directs the immune response to multiple peptide sequencesthat are actually present in native 151P3D4, thus avoiding the need toevaluate any junctional epitopes. Lastly, the embodiment provides aneconomy of scale when producing peptide or nucleic acid vaccinecompositions.

[0655] Related to this embodiment, computer programs are available inthe art which can be used to identify in a target sequence, the greatestnumber of epitopes per sequence length.

Example 26

[0656] Polyepitopic Vaccine Compositions from Multiple Antigens

[0657] The 151P3D4 peptide epitopes of the present invention are used inconjunction with epitopes from other target tumor-associated antigens,to create a vaccine composition that is useful for the prevention ortreatment of cancer that expresses 151P3D4 and such other antigens. Forexample, a vaccine composition can be provided as a single polypeptidethat incorporates multiple epitopes from 151P3D4 as well astumor-associated antigens that are often expressed with a target cancerassociated with 151P3D4 expression, or can be administered as acomposition comprising a cocktail of one or more discrete epitopes.Alternatively, the vaccine can be administered as a minigene constructor as dendritic cells which have been loaded with the peptide epitopesin vitro.

Example 27

[0658] Use of Peptides to Evaluate an Immune Response

[0659] Peptides of the invention may be used to analyze an immuneresponse for the presence of specific antibodies, CTL or HTL directed to151P3D4. Such an analysis can be performed in a manner described by Ogget al., Science 279:2103-2106, 1998. In this Example, peptides inaccordance with the invention are used as a reagent for diagnostic orprognostic purposes, not as an immunogen.

[0660] In this example highly sensitive human leukocyte antigentetrameric complexes (“tetramers”) are used for a cross-sectionalanalysis of, for example, 151P3D4 HLA-A*0201-specific CTL frequenciesfrom HLA A*0201-positive individuals at different stages of disease orfollowing immunization comprising a 151P3D4 peptide containing an A*0201motif Tetrameric complexes are synthesized as described (Musey et al.,N. Engl. J. Med. 337:1267, 1997). Briefly, purified HLA heavy chain(A*0201 in this example) and β2-microglobulin are synthesized by meansof a prokaryotic expression system. The heavy chain is modified bydeletion of the transmembrane-cytosolic tail and COOH-terminal additionof a sequence containing a BirA enzymatic biotinylation site. The heavychain, β2-microglobulin, and peptide are refolded by dilution. The 45-kDrefolded product is isolated by fast protein liquid chromatography andthen biotinylated by BirA in the presence of biotin (Sigma, St. Louis,Mo.), adenosine 5′ triphosphate and magnesium.Streptavidin-phycoerythrin conjugate is added in a 1:4 molar ratio, andthe tetrameric product is concentrated to 1 mg/ml. The resulting productis referred to as tetramer-phycoerythrin.

[0661] For the analysis of patient blood samples, approximately onemillion PBMCs are centrifuged at 300 g for 5 minutes and resuspended in50 μl of cold phosphate-buffered saline. Tri-color analysis is performedwith the tetramer-phycoerythrin, along with anti-CD8-Tricolor, andanti-CD38. The PBMCs are incubated with tetramer and antibodies on icefor 30 to 60 min and then washed twice before formaldehyde fixation.Gates are applied to contain >99.98% of control samples. Controls forthe tetramers include both A*0201-negative individuals andA*0201-positive non-diseased donors. The percentage of cells stainedwith the tetramer is then determined by flow cytometry. The resultsindicate the number of cells in the PBMC sample that containepitope-restricted CTLs, thereby readily indicating the extent of immuneresponse to the 151P3D4 epitope, and thus the status of exposure to151P3D4, or exposure to a vaccine that elicits a protective ortherapeutic response.

Example 28

[0662] Use of Peptide Epitopes to Evaluate Recall Responses

[0663] The peptide epitopes of the invention are used as reagents toevaluate T cell responses, such as acute or recall responses, inpatients. Such an analysis may be performed on patients who haverecovered from 151P3D4-associated disease or who have been vaccinatedwith a 151P3D4 vaccine.

[0664] For example, the class I restricted CTL response of persons whohave been vaccinated may be analyzed. The vaccine may be any 151P3D4vaccine. PBMC are collected from vaccinated individuals and HLA typed.Appropriate peptide epitopes of the invention that, optimally, bearsupermotifs to provide cross-reactivity with multiple HLA supertypefamily members, are then used for analysis of samples derived fromindividuals who bear that HLA type.

[0665] PBMC from vaccinated individuals are separated onFicoll-Histopaque density gradients (Sigma Chemical Co., St. Louis,Mo.), washed three times in HBSS (GIBCO Laboratories), resuspended inRPMI-1640 (GIBCO Laboratories) supplemented with L-glutamine (2 mM),penicillin (50 U/ml), streptomycin (50 μg/ml), and Hepes (10 mM)containing 10% heat-inactivated human AB serum (complete RPMI) andplated using microculture formats. A synthetic peptide comprising anepitope of the invention is added at 10 μg/ml to each well and HBV core128-140 epitope is added at 1 μg/ml to each well as a source of T cellhelp during the first week of stimulation.

[0666] In the microculture format, 4×10⁵ PBMC are stimulated withpeptide in 8 replicate cultures in 96-well round bottom plate in 100μl/well of complete RPMI. On days 3 and 10, 100 μl of complete RPMI and20 U/ml final concentration of rIL-2 are added to each well. On day 7the cultures are transferred into a 96-well flat-bottom plate andrestimulated with peptide, rIL-2 and 10⁵ irradiated (3,000 rad)autologous feeder cells. The cultures are tested for cytotoxic activityon day 14. A positive CTL response requires two or more of the eightreplicate cultures to display greater than 10% specific ⁵¹Cr release,based on comparison with non-diseased control subjects as previouslydescribed (Rehermann, et al., Nature Med. 2:1104,1108, 1996; Rehermannet al., J. Clin. Invest. 97:1655-1665, 1996; and Rehermann et al. J.Clin. Invest. 98:1432-1440, 1996).

[0667] Target cell lines are autologous and allogeneic EBV-transformedB-LCL that are either purchased from the American Society forHistocompatibility and Immunogenetics (ASHI, Boston, Mass.) orestablished from the pool of patients as described (Guilhot, et al. J.Virol. 66:2670-2678, 1992).

[0668] Cytotoxicity assays are performed in the following manner. Targetcells consist of either allogeneic HLA-matched or autologousEBV-transformed B lymphoblastoid cell line that are incubated overnightwith the synthetic peptide epitope of the invention at 10 μM, andlabeled with 100 μCi of ⁵¹Cr (Amersham Corp., Arlington Heights, Ill.)for 1 hour after which they are washed four times with HBSS.

[0669] Cytolytic activity is determined in a standard 4-h, split well⁵¹Cr release assay using U-bottomed 96 well plates containing 3,000targets/well. Stimulated PBMC are tested at effector/target (E/T) ratiosof 20-50:1 on day 14. Percent cytotoxicity is determined from theformula: 100×[(experimental release-spontaneous release)/maximumrelease-spontaneous release)]. Maximum release is determined by lysis oftargets by detergent (2% Triton X-100; Sigma Chemical Co., St. Louis,Mo.). Spontaneous release is <25% of maximum release for allexperiments.

[0670] The results of such an analysis indicate the extent to whichHLA-restricted CTL populations have been stimulated by previous exposureto 151P3D4 or a 151P3D4 vaccine.

[0671] Similarly, Class II restricted HTL responses may also beanalyzed. Purified PBMC are cultured in a 96-well flat bottom plate at adensity of 1.5×10⁵ cells/well and are stimulated with 10 μg/ml syntheticpeptide of the invention, whole 151P3D4 antigen, or PHA. Cells areroutinely plated in replicates of 4-6 wells for each condition. Afterseven days of culture, the medium is removed and replaced with freshmedium containing 10 U/ml IL-2. Two days later, 1 μCi ³H-thymidine isadded to each well and incubation is continued for an additional 18hours. Cellular DNA is then harvested on glass fiber mats and analyzedfor ³H-thymidine incorporation. Antigen-specific T cell proliferation iscalculated as the ratio of ³H-thymidine incorporation in the presence ofantigen divided by the ³H-thymidine incorporation in the absence ofantigen.

Example 29

[0672] Induction of Specific CTL Response in Humans

[0673] A human clinical trial for an immunogenic composition comprisingCTL and HTL epitopes of the invention is set up as an IND Phase I, doseescalation study and carried out as a randomized, double-blind,placebo-controlled trial. Such a trial is designed, for example, asfollows:

[0674] A total of about 27 individuals are enrolled and divided into 3groups:

[0675] Group I: 3 subjects are injected with placebo and 6 subjects areinjected with 5 μg of peptide composition;

[0676] Group II: 3 subjects are injected with placebo and 6 subjects areinjected with 50 μg peptide composition;

[0677] Group III: 3 subjects are injected with placebo and 6 subjectsare injected with 500 μg of peptide composition.

[0678] After 4 weeks following the first injection, all subjects receivea booster inoculation at the same dosage.

[0679] The endpoints measured in this study relate to the safety andtolerability of the peptide composition as well as its immunogenicity.Cellular immune responses to the peptide composition are an index of theintrinsic activity of this the peptide composition, and can therefore beviewed as a measure of biological efficacy. The following summarize theclinical and laboratory data that relate to safety and efficacyendpoints.

[0680] Safety: The incidence of adverse events is monitored in theplacebo and drug treatment group and assessed in terms of degree andreversibility.

[0681] Evaluation of Vaccine Efficacy: For evaluation of vaccineefficacy, subjects are bled before and after injection. Peripheral bloodmononuclear cells are isolated from fresh heparinized blood byFicoll-Hypaque density gradient centrifugation, aliquoted in freezingmedia and stored frozen. Samples are assayed for CTL and HTL activity.

[0682] The vaccine is found to be both safe and efficacious.

Example 30

[0683] Phase II Trials in Patients Expressing 151P3D4

[0684] Phase II trials are performed to study the effect ofadministering the CTL-HTL peptide compositions to patients having cancerthat expresses 151P3D4. The main objectives of the trial are todetermine an effective dose and regimen for inducing CTLs in cancerpatients that express 151P3D4, to establish the safety of inducing a CTLand HTL response in these patients, and to see to what extent activationof CTLs improves the clinical picture of these patients, as manifested,e.g., by the reduction and/or shrinking of lesions. Such a study isdesigned, for example, as follows:

[0685] The studies are performed in multiple centers. The trial designis an open-label, uncontrolled, dose escalation protocol wherein thepeptide composition is administered as a single dose followed six weekslater by a single booster shot of the same dose. The dosages are 50, 500and 5,000 micrograms per injection. Drug-associated adverse effects(severity and reversibility) are recorded.

[0686] There are three patient groupings. The first group is injectedwith 50 micrograms of the peptide composition and the second and thirdgroups with 500 and 5,000 micrograms of peptide composition,respectively. The patients within each group range in age from 21-65 andrepresent diverse ethnic backgrounds. All of them have a tumor thatexpresses 151P3D4.

[0687] Clinical manifestations or antigen-specific T-cell responses aremonitored to assess the effects of administering the peptidecompositions. The vaccine composition is found to be both safe andefficacious in the treatment of 151P3D4-associated disease.

Example 31

[0688] Induction of CTL Responses Using a Prime Boost Protocol

[0689] A prime boost protocol similar in its underlying principle tothat used to confirm the efficacy of a DNA vaccine in transgenic mice,such as described above in the Example entitled “The Plasmid Constructand the Degree to Which It Induces Immunogenicity,” can also be used forthe administration of the vaccine to humans. Such a vaccine regimen caninclude an initial administration of, for example, naked DNA followed bya boost using recombinant virus encoding the vaccine, or recombinantprotein/polypeptide or a peptide mixture administered in an adjuvant.

[0690] For example, the initial immunization may be performed using anexpression vector, such as that constructed in the Example entitled“Construction of “Minigene” Multi-Epitope DNA Plasmids” in the form ofnaked nucleic acid administered IM (or SC or ID) in the amounts of 0.5-5mg at multiple sites. The nucleic acid (0.1 to 1000 μg) can also beadministered using a gene gun. Following an incubation period of 3-4weeks, a booster dose is then administered. The booster can berecombinant fowlpox virus administered at a dose of 5-10⁷ to 5×10⁹ pfu.An alternative recombinant virus, such as an MVA, canarypox, adenovirus,or adeno-associated virus, can also be used for the booster, or thepolyepitopic protein or a mixture of the peptides can be administered.For evaluation of vaccine efficacy, patient blood samples are obtainedbefore immunization as well as at intervals following administration ofthe initial vaccine and booster doses of the vaccine. Peripheral bloodmononuclear cells are isolated from fresh heparinized blood byFicoll-Hypaque density gradient centrifugation, aliquoted in freezingmedia and stored frozen. Samples are assayed for CTL and HTL activity.

[0691] Analysis of the results indicates that a magnitude of responsesufficient to achieve a therapeutic or protective immunity against151P3D4 is generated.

Example 32

[0692] Administration of Vaccine Compositions Using Dendritic Cells (DC)

[0693] Vaccines comprising peptide epitopes of the invention can beadministered using APCs, or “professional” APCs such as DC. In thisexample, peptide-pulsed DC are administered to a patient to stimulate aCTL response in vivo. In this method, dendritic cells are isolated,expanded, and pulsed with a vaccine comprising peptide CTL and HTLepitopes of the invention. The dendritic cells are infused back into thepatient to elicit CTL and HTL responses in vivo. The induced CTL and HTLthen destroy or facilitate destruction, respectively, of the targetcells that bear the 151P3D4 protein from which the epitopes in thevaccine are derived.

[0694] For example, a cocktail of epitope-comprising peptides isadministered ex vivo to PBMC, or isolated DC therefrom. A pharmaceuticalto facilitate harvesting of DC can be used, such as Progenipoietin™(Monsanto, St. Louis, Mo.) or GM-CSF/IL-4. After pulsing the DC withpeptides, and prior to reinfusion into patients, the DC are washed toremove unbound peptides.

[0695] As appreciated clinically, and readily determined by one of skillbased on clinical outcomes, the number of DC reinfused into the patientcan vary (see, e.g., Nature Med. 4:328, 1998; Nature Med. 2:52, 1996 andProstate 32:272, 1997). Although 2-50×10⁶ DC per patient are typicallyadministered, larger number of DC, such as 10⁷ or 10⁸ can also beprovided. Such cell populations typically contain between 50-90% DC.

[0696] In some embodiments, peptide-loaded PBMC are injected intopatients without purification of the DC. For example, PBMC generatedafter treatment with an agent such as Progenipoietin™ are injected intopatients without purification of the DC. The total number of PBMC thatare administered often ranges from 10⁸ to 10¹⁰. Generally, the celldoses injected into patients is based on the percentage of DC in theblood of each patient, as determined, for example, by immunofluorescenceanalysis with specific anti-DC antibodies. Thus, for example, ifProgenipoietin™ mobilizes 2% DC in the peripheral blood of a givenpatient, and that patient is to receive 5×10⁶ DC, then the patient willbe injected with a total of 2.5×10⁸ peptide-loaded PBMC. The percent DCmobilized by an agent such as Progenipoietin™ is typically estimated tobe between 2-10%, but can vary as appreciated by one of skill in theart.

[0697] Ex vivo activation of CTL/HTL responses

[0698] Alternatively, ex vivo CTL or HTL responses to 151P3D4 antigenscan be induced by incubating, in tissue culture, the patient's, orgenetically compatible, CTL or HTL precursor cells together with asource of APC, such as DC, and immunogenic peptides. After anappropriate incubation time (typically about 7-28 days), in which theprecursor cells are activated and expanded into effector cells, thecells are infused into the patient, where they will destroy (CTL) orfacilitate destruction (HTL) of their specific target cells, i.e., tumorcells.

Example 33

[0699] An Alternative Method of Identifying and Confirming Motif-BearingPeptides

[0700] Another method of identifying and confirming motif-bearingpeptides is to elute them from cells bearing defined MHC molecules. Forexample, EBV transformed B cell lines used for tissue typing have beenextensively characterized to determine which HLA molecules they express.In certain cases these cells express only a single type of HLA molecule.These cells can be transfected with nucleic acids that express theantigen of interest, e.g. 151P3D4. Peptides produced by endogenousantigen processing of peptides produced as a result of transfection willthen bind to HLA molecules within the cell and be transported anddisplayed on the cell's surface. Peptides are then eluted from the HLAmolecules by exposure to mild acid conditions and their amino acidsequence determined, e.g., by mass spectral analysis (e.g., Kubo et al.,J. Immunol. 152:3913, 1994). Because the majority of peptides that binda particular HLA molecule are motif-bearing, this is an alternativemodality for obtaining the motif-bearing peptides correlated with theparticular HLA molecule expressed on the cell.

[0701] Alternatively, cell lines that do not express endogenous HLAmolecules can be transfected with an expression construct encoding asingle HLA allele. These cells can then be used as described, i.e., theycan then be transfected with nucleic acids that encode 151P3D4 toisolate peptides corresponding to 151P3D4 that have been presented onthe cell surface. Peptides obtained from such an analysis will bearmotif(s) that correspond to binding to the single HLA allele that isexpressed in the cell.

[0702] As appreciated by one in the art, one can perform a similaranalysis on a cell bearing more than one HLA allele and subsequentlydetermine peptides specific for each HLA allele expressed. Moreover, oneof skill would also recognize that means other than transfection, suchas loading with a protein antigen, can be used to provide a source ofantigen to the cell.

Example 34

[0703] Complementary Polynucleotides

[0704] Sequences complementary to the 151P3D4-encoding sequences, or anyparts thereof, are used to detect, decrease, or inhibit expression ofnaturally occurring 151P3D4. Although use of oligonucleotides comprisingfrom about 15 to 30 base pairs is described, essentially the sameprocedure is used with smaller or with larger sequence fragments.Appropriate oligonucleotides are designed using, e.g., OLIGO 4.06software (National Biosciences) and the coding sequence of 151P3D4. Toinhibit transcription, a complementary oligonucleotide is designed fromthe most unique 5′ sequence and used to prevent promoter binding to thecoding sequence. To inhibit translation, a complementary oligonucleotideis designed to prevent ribosomal binding to a 151P3D4-encodingtranscript.

Example 35

[0705] Purification of Naturally-Occurring or Recombinant 151P3D4 Using151P3D4-Specific Antibodies

[0706] Naturally occurring or recombinant 151P3D4 is substantiallypurified by immunoaffinity chromatography using antibodies specific for151P3D4. An immunoaffinity column is constructed by covalently couplinganti-151P3D4 antibody to an activated chromatographic resin, such asCNBr-activated SEPHAROSE (Amersham Pharmacia Biotech). After thecoupling, the resin is blocked and washed according to themanufacturer's instructions.

[0707] Media containing 151P3D4 are passed over the immunoaffinitycolumn, and the column is washed under conditions that allow thepreferential absorbance of 151P3D4 (e.g., high ionic strength buffers inthe presence of detergent). The column is eluted under conditions thatdisrupt antibody/151P3D4 binding (e.g., a buffer of pH 2 to pH 3, or ahigh concentration of a chaotrope, such as urea or thiocyanate ion), andGCR.P is collected.

Example 36

[0708] Identification of Molecules Which Interact with 151P3D4

[0709] 151P3D4, or biologically active fragments thereof, are labeledwith 121 1 Bolton-Hunter reagent. (See, e.g., Bolton et al. (1973)Biochem. J. 133:529.) Candidate molecules previously arrayed in thewells of a multi-well plate are incubated with the labeled 151P3D4,washed, and any wells with labeled 151P3D4 complex are assayed. Dataobtained using different concentrations of 151P3D4 are used to calculatevalues for the number, affinity, and association of 151P3D4 with thecandidate molecules.

Example 37

[0710] In vivo Assay for 151P3D4 Tumor Growth Promotion

[0711] The effect of the 151P3D4 protein on tumor cell growth isevaluated in vivo by evaluating tumor development and growth of cellsexpressing or lacking 151P3D4. For example, SCID mice are injectedsubcutaneously on each flank with 1×10⁶ of either 3T3, bladder, kidneyor ovary cancer cell lines (e.g. SCABER, J82, PA-1, CaOv3, A498 or 769Pcells) containing tkNeo empty vector or 151P3D4. At least two strategiesmay be used: (1) Constitutive 151P3D4 expression under regulation of apromoter such as a constitutive promoter obtained from the genomes ofviruses such as polyoma virus, fowlpox virus (UK 2,211,504 publishedJul. 5, 1989), adenovirus (such as Adenovirus 2), bovine papillomavirus, avian sarcoma virus, cytomegalovirus, a retrovirus, hepatitis-Bvirus and Simian Virus 40 (SV40), or from heterologous mammalianpromoters, e.g., the actin promoter or an immunoglobulin promoter,provided such promoters are compatible with the host cell systems, and(2) Regulated expression under control of an inducible vector system,such as ecdysone, tetracycline, etc., provided such promoters arecompatible with the host cell systems. Tumor volume is then monitored bycaliper measurement at the appearance of palpable tumors and followedover time to determine if 151P3D4-expressing cells grow at a faster rateand whether tumors produced by 151P3D4-expressing cells demonstratecharacteristics of altered aggressiveness (e.g. enhanced metastasis,vascularization, reduced responsiveness to chemotherapeutic drugs).

[0712] Additionally, mice can be implanted with 1×10⁵ of the same cellsorthotopically to determine if 151P3D4 has an effect on local growth inthe bladder, kidney or ovary, and whether 151P3D4 affects the ability ofthe cells to metastasize, specifically to lymph nodes, adrenal, liverand bone (Miki T et al, Oncol Res. 2001;12:209; Fu X et al, Int JCancer. 1991, 49:938; Kiguchi Ket al, Clin Exp Metastasis. 1998,16:751).

[0713] The assay is also useful to determine the 151P3D4 inhibitoryeffect of candidate therapeutic compositions, such as for example,151P3D4 intrabodies, 151P3D4 antisense molecules and ribozymes.

Example 38

[0714] 151P3D4 Monoclonal Antibody-Mediated Inhibition of Bladder,Kidney and Ovarian Tumors In Vivo

[0715] The significant expression of 151P3D4 in cancer tissues, togetherwith its restrictive expression in normal tissues makes 151P3D4 a goodtarget for antibody therapy. Similarly, 151P3D4 is a target for Tcell-based immunotherapy. Thus, the therapeutic efficacy of anti-151P3D4mAbs in human bladder cancer xenograft mouse models is evaluated byusing recombinant cell lines such as SCABER-151P3D4, J82-151P3D4, and3T3-151P3D4 (see, e.g., Kaighn, M. E., et al., Invest Urol, 1979. 17(1):p. 16-23). Similarly anti-151P3D4 mAbs are evaluated in human kidney andovarian cancer xenograft models using recombinant cell lines such asA498-151P3D4 and PA1-151P3D4.

[0716] Antibody efficacy on tumor growth and metastasis formation isstudied, e.g., in a mouse orthotopic bladder cancer xenograft model, amouse kidney cancer xenograft model and a mouse ovarian cancer xenograftmodel. The antibodies can be unconjugated, as discussed in this Example,or can be conjugated to a therapeutic modality, as appreciated in theart. Anti-151P3D4 mAbs inhibit formation of kidney, ovarian and bladderxenografts. Anti-151P3D4 mAbs also retard the growth of establishedorthotopic tumors and prolonged survival of tumor-bearing nice. Theseresults indicate the utility of anti-151P3D4 mAbs in the treatment oflocal and advanced stages of ovarian, kidney and bladder cancer. (See,e.g., Saffran, D., et al., PNAS 10:1073-1078 orwww.pnas.org/cgi/doi/10.1073/pnas.051624698).

[0717] Administration of the anti-151P3D4 mAbs led to retardation ofestablished orthotopic tumor growth and inhibition of metastasis todistant sites, resulting in a significant prolongation in the survivalof tumor-bearing mice. These studies indicate that 151P3D4 as anattractive target for immunotherapy and demonstrate the therapeuticpotential of anti-151P3D4 mAbs for the treatment of local and metastaticcancer. This example demonstrates that unconjugated 151P3D4 monoclonalantibodies are effective to inhibit the growth of human bladder, kidneyand ovarian tumor xenografts grown in SCID mice; accordingly acombination of such efficacious monoclonal antibodies is also effective.

[0718] Tumor Inhibition Using Multiple Unconjugated 151P3D4 mAbs

[0719] Materials and Methods

[0720] 151P3D4 Monoclonal Antibodies:

[0721] Monoclonal antibodies are raised against 151P3D4 as described inthe Example entitled “Generation of 151P3D4 Monoclonal Antibodies(mAbs).” The antibodies are characterized by ELISA, Western blot, FACS,and immunoprecipitation for their capacity to bind 151P3D4. Epitopemapping data for the anti-151P3D4 mAbs, as determined by ELISA andWestern analysis, recognize epitopes on the 151P3D4 protein.Immunohistochemical analysis of prostate cancer tissues and cells withthese antibodies is performed.

[0722] The monoclonal antibodies are purified from ascites or hybridomatissue culture supernatants by Protein-G Sepharose chromatography,dialyzed against PBS, filter sterilized, and stored at −20° C. Proteindeterminations are performed by a Bradford assay (Bio-Rad, Hercules,Calif.). A therapeutic monoclonal antibody or a cocktail comprising amixture of individual monoclonal antibodies is prepared and used for thetreatment of mice receiving subcutaneous or orthotopic injections ofSCABER, J82, A498, 769P, CaOv1 or PA1 tumor xenografts.

[0723] Cell Lines

[0724] The bladder, kidney and ovary carcinoma cell lines, SCABER, J82,A498, 769P, CaOv1 and PA1 as well as the fibroblast line NIH 3T3(American Type Culture Collection) are maintained in DMEM supplementedwith L-glutamine and 10% FBS.

[0725] A SCABER-151P3D4, J82-151P3D4, A498-151P3D4, 769P-151P3D4,CaOv1-151P3D4, PA1-151P3D4 and 3T3-151P3D4 cell populations aregenerated by retroviral gene transfer as described in Hubert, R. S., etal., Proc Natl Acad Sci USA, 1999. 96(25): 14523.

[0726] Xenograft Mouse Models.

[0727] Subcutaneous (s.c.) tumors are generated by injection of 1×10⁶cancer cells mixed at a 1:1 dilution with Matrigel (CollaborativeResearch) in the right flank of male SCID mice. To test antibodyefficacy on tumor formation, i.p. antibody injections are started on thesame day as tumor-cell injections. As a control, mice are injected witheither purified mouse IgG (ICN) or PBS; or a purified monoclonalantibody that recognizes an irrelevant antigen not expressed in humancells. Tumor sizes are determined by caliper measurements, and the tumorvolume is calculated as: Length×Width×Height. Mice with s.c. tumorsgreater than 1.5 cm in diameter are sacrificed.

[0728] Orthotopic injections are performed under anesthesia by usingketamine/xylazine. For bladder orthotopic studies, an incision is madethrough the abdomen to expose the bladder, and tumor cells (5×10⁵) mixedwith Matrigel are injected into the bladder wall in a 10-μl volume. Tomonitor tumor growth, mice are palpated and blood is collected on aweekly basis to measure BTA levels. For kidney and ovary orthopoticmodels, an incision is made through the abdominal muscles to expose thekidney or the ovary. Tumor cells mixed with Matrigel are injected underthe kidney capsule or into the ovary in a 10-μl volume (Yoshida Y et al,Anticancer Res. 1998, 18:327; Ahn et al, Tumour Biol. 2001, 22:146). Tomonitor tumor growth, blood is collected on a weekly basis measuringG250 and SM047 levels. The mice are segregated into groups for theappropriate treatments, with anti-151P3D4 or control mAbs being injectedi.p.

[0729] Anti-151P3D4 mAbs Inhibit Growth of 151P3D4-ExpressingXenograft-Cancer Tumors

[0730] The effect of anti-151P3D4 mAbs on tumor formation is tested onthe growth and progression of bladder, kidney and ovarian cancerxenografts using UC3-151P3D4, J82-151P3D4, A498-151P3D4, 769P-151P3D4,CaOv1-151P3D4 and PA1-151P3D4 orthotopic models. As compared with thes.c. tumor model, the orthotopic model, which requires injection oftumor cells directly in the mouse bladder, kidney and ovary,respectively, results in a local tumor growth, development of metastasisin distal sites, deterioration of mouse health, and subsequent death(Saffran, D., et al., PNAS supra; Fu, X., et al., Int J Cancer, 1992.52(6): p. 987-90; Kubota, T., J Cell Biochem, 1994. 56(1): p. 4-8). Thefeatures make the orthotopic model more representative of human diseaseprogression and allowed us to follow the therapeutic effect of mAbs onclinically relevant end points.

[0731] Accordingly, tumor cells are injected into the mouse bladder,kidney or ovary, and 2 days later, the mice are segregated into twogroups and treated with either: a) 200-500 μg, of anti-151P3D4 Ab, or b)PBS three times per week for two to five weeks.

[0732] A major advantage of the orthotopic cancer models is the abilityto study the development of metastases. Formation of metastasis in micebearing established orthotopic tumors is studies by IHC analysis on lungsections using an antibody against a tumor-specific cell-surface proteinsuch as anti-CK20 for bladder cancer, anti-G250 for kidney cancer andSM047 antibody for ovarian cancer models (Lin S et al, Cancer DetectPrev. 2001;25:202; McCluggage W et al, Histopathol 2001, 38:542).

[0733] Mice bearing established orthotopic tumors are administered 1000μg injections of either anti-151P3D4 mAb or PBS over a 4-week period.Mice in both groups are allowed to establish a high tumor burden, toensure a high frequency of metastasis formation in mouse lungs. Micethen are killed and their bladders, livers, bone and lungs are analyzedfor the presence of tumor cells by IHC analysis.

[0734] These studies demonstrate a broad anti-tumor efficacy ofanti-151P3D4 antibodies on initiation and progression of prostate andkidney cancer in xenograft mouse models. Anti-151P3D4 antibodies inhibittumor formation of tumors as well as retarding the growth of alreadyestablished tumors and prolong the survival of treated mice. Moreover,anti-151P3D4 mAbs demonstrate a dramatic inhibitory effect on the spreadof local bladder, kidney and ovarian tumor to distal sites, even in thepresence of a large tumor burden. Thus, anti-151P3D4 mAbs areefficacious on major clinically relevant end points (tumor growth),prolongation of survival, and health.

Example 39

[0735] Therapeutic and Diagnostic Use of Anti-151P3D4 Antibodies inHumans.

[0736] Anti-151P3D4 monoclonal antibodies are safely and effectivelyused for diagnostic, prophylactic, prognostic and/or therapeuticpurposes in humans. Western blot and immunohistochemical analysis ofcancer tissues and cancer xenografts with anti-151P3D4 mAb show strongextensive staining in carcinoma but significantly lower or undetectablelevels in normal tissues. Detection of 151P3D4 in carcinoma and inmetastatic disease demonstrates the usefulness of the mAb as adiagnostic and/or prognostic indicator. Anti-151P3D4 antibodies aretherefore used in diagnostic applications such as immunohistochemistryof kidney biopsy specimens to detect cancer from suspect patients.

[0737] As determined by flow cytometry, anti-151P3D4 mAb specificallybinds to carcinoma cells. Thus, anti-151P3D4 antibodies are used indiagnostic whole body imaging applications, such asradioimmunoscintigraphy and radioimmunotherapy, (see, e.g., PotamianosS., et. al. Anticancer Res 20(2A):925-948 (2000)) for the detection oflocalized and metastatic cancers that exhibit expression of 151P3D4.Shedding or release of an extracellular domain of 151P3D4 into theextracellular milieu, such as that seen for alkaline phosphodiesteraseB10 (Meerson, N. R., Hepatology 27:563-568 (1998)), allows diagnosticdetection of 151P3D4 by anti-151P3D4 antibodies in serum and/or urinesamples from suspect patients.

[0738] Anti-151P3D4 antibodies that specifically bind 151P3D4 are usedin therapeutic applications for the treatment of cancers that express151P3D4. Anti-151P3D4 antibodies are used as an unconjugated modalityand as conjugated form in which the antibodies are attached to one ofvarious therapeutic or imaging modalities well known in the art, such asa prodrugs, enzymes or radioisotopes. In preclinical studies,unconjugated and conjugated anti-151P3D4 antibodies are tested forefficacy of tumor prevention and growth inhibition in the SCID mousecancer xenograft models, e.g., kidney cancer models AGS-K3 and AGS-K6,(see, e.g., the Example entitled “151P3D4 Monoclonal Antibody-mediatedInhibition of Bladder and Lung Tumors In Vivo”). Conjugated andunconjugated anti-151P3D4 antibodies are used as a therapeutic modalityin human clinical trials either alone or in combination with othertreatments as described in following Examples.

Example 40

[0739] Human Clinical Trials for the Treatment and Diagnosis of HumanCarcinomas Through Use of Human Anti-151P3D4 Antibodies In Vivo

[0740] Antibodies are used in accordance with the present inventionwhich recognize an epitope on 151P3D4, and are used in the treatment ofcertain tumors such as those listed in Table I. Based upon a number offactors, including 151P3D4 expression levels, tumors such as thoselisted in Table I are presently preferred indications. In connectionwith each of these indications, three clinical approaches aresuccessfully pursued.

[0741] I.) Adjunctive therapy: In adjunctive therapy, patients aretreated with anti-151P3D4 antibodies in combination with achemotherapeutic or antineoplastic agent and/or radiation therapy.Primary cancer targets, such as those listed in Table I, are treatedunder standard protocols by the addition anti-151P3D4 antibodies tostandard first and second line therapy. Protocol designs addresseffectiveness as assessed by reduction in tumor mass as well as theability to reduce usual doses of standard chemotherapy. These dosagereductions allow additional and/or prolonged therapy by reducingdose-related toxicity of the chemotherapeutic agent. Anti-151P3D4antibodies are utilized in several adjunctive clinical trials incombination with the chemotherapeutic or antineoplastic agentsadriamycin (advanced prostrate carcinoma), cisplatin (advanced head andneck and lung carcinomas), taxol (breast cancer), and doxorubicin(preclinical).

[0742] II.) Monotherapy: In connection with the use of the anti-151P3D4antibodies in monotherapy of tumors, the antibodies are administered topatients without a chemotherapeutic or antineoplastic agent. In oneembodiment, monotherapy is conducted clinically in end stage cancerpatients with extensive metastatic disease. Patients show some diseasestabilization. Trials demonstrate an effect in refractory patients withcancerous tumors.

[0743] III.) Imaging Agent: Through binding a radionuclide (e.g., iodineor yttrium (I¹³¹, Y⁹⁰) to anti-151P3D4 antibodies, the radiolabeledantibodies are utilized as a diagnostic and/or imaging agent. In such arole, the labeled antibodies localize to both solid tumors, as well as,metastatic lesions of cells expressing 151P3D4. In connection with theuse of the anti-151P3D4 antibodies as imaging agents, the antibodies areused as an adjunct to surgical treatment of solid tumors, as both apre-surgical screen as well as a post-operative follow-up to determinewhat tumor remains and/or returns. In one embodiment, a (¹¹¹ In)-151P3D4antibody is used as an imaging agent in a Phase I human clinical trialin patients having a carcinoma that expresses 151P3D4 (by analogy see,e.g., Divgi et al. J. Natl. Cancer Inst. 83:97-104 (1991)). Patients arefollowed with standard anterior and posterior gamma camera. The resultsindicate that primary lesions and metastatic lesions are identified

[0744] Dose and Route of Administration

[0745] As appreciated by those of ordinary skill in the art, dosingconsiderations can be determined through comparison with the analogousproducts that are in the clinic. Thus, anti-151P3D4 antibodies can beadministered with doses in the range of 5 to 400 mg/m², with the lowerdoses used, e.g., in connection with safety studies. The affinity ofanti-151P3D4 antibodies relative to the affinity of a known antibody forits target is one parameter used by those of skill in the art fordetermining analogous dose regimens. Further, anti-151P3D4 antibodiesthat are fully human antibodies, as compared to the chimeric antibody,have slower clearance; accordingly, dosing in patients with such fullyhuman anti-151P3D4 antibodies can be lower, perhaps in the range of 50to 300 mg/m², and still remain efficacious. Dosing in mg/m², as opposedto the conventional measurement of dose in mg/kg, is a measurement basedon surface area and is a convenient dosing measurement that is designedto include patients of all sizes from infants to adults.

[0746] Three distinct delivery approaches are useful for delivery ofanti-151P3D4 antibodies. Conventional intravenous delivery is onestandard delivery technique for many tumors. However, in connection withtumors in the peritoneal cavity, such as tumors of the ovaries, biliaryduct, other ducts, and the like, intraperitoneal administration mayprove favorable for obtaining high dose of antibody at the tumor and toalso minimize antibody clearance. In a similar manner, certain solidtumors possess vasculature that is appropriate for regional perfusion.Regional perfusion allows for a high dose of antibody at the site of atumor and minimizes short term clearance of the antibody.

[0747] Clinical Development Plan (CDP)

[0748] Overview: The CDP follows and develops treatments of anti-151P3D4antibodies in connection with adjunctive therapy, monotherapy, and as animaging agent. Trials initially demonstrate safety and thereafterconfirm efficacy in repeat doses. Trails are open label comparingstandard chemotherapy with standard therapy plus anti-151P3D4antibodies. As will be appreciated, one criteria that can be utilized inconnection with enrollment of patients is 151P3D4 expression levels intheir tumors as determined by biopsy.

[0749] As with any protein or antibody infusion-based therapeutic,safety concerns are related primarily to (i) cytokine release syndrome,i.e., hypotension, fever, shaking, chills; (ii) the development of animmunogenic response to the material (i.e., development of humanantibodies by the patient to the antibody therapeutic, or HAHAresponse); and, (iii) toxicity to normal cells that express 151P3D4.Standard tests and follow-up are utilized to monitor each of thesesafety concerns. Anti-151P3D4 antibodies are found to be safe upon humanadministration.

Example 41

[0750] Human Clinical Trial Adjunctive Therapy with Human Anti-151P3D4Antibody and Chemotherapeutic Agent

[0751] A phase I human clinical trial is initiated to assess the safetyof six intravenous doses of a human anti-151P3D4 antibody in connectionwith the treatment of a solid tumor, e.g., a cancer of a tissue listedin Table I. In the study, the safety of single doses of anti-151P3D4antibodies when utilized as an adjunctive therapy to an antineoplasticor chemotherapeutic agent, such as cisplatin, topotecan, doxorubicin,adriamycin, taxol, or the like, is assessed. The trial design includesdelivery of six single doses of an anti-151P3D4 antibody with dosage ofantibody escalating from approximately about 25 mg/m² to about 275 mg/m²over the course of the treatment in accordance with the followingschedule: Day 0 Day 7 Day 14 Day 21 Day 28 Day 35 mAb Dose 25 mg/m² 75mg/m² 125 mg/m² 175 mg/m² 225 mg/m² 275 mg/m² Chemotherapy + + + + + +(standard dose)

[0752] Patients are closely followed for one-week following eachadministration of antibody and chemotherapy. In particular, patients areassessed for the safety concerns mentioned above: (i) cytokine releasesyndrome, i.e., hypotension, fever, shaking, chills; (ii) thedevelopment of an immunogenic response to the material (i.e.,development of human antibodies by the patient to the human antibodytherapeutic, or HAHA response); and, (iii) toxicity to normal cells thatexpress 151P3D4. Standard tests and follow-up are utilized to monitoreach of these safety concerns. Patients are also assessed for clinicaloutcome, and particularly reduction in tumor mass as evidenced by MRI orother imaging.

[0753] The anti-151P3D4 antibodies are demonstrated to be safe andefficacious, Phase II trials confirm the efficacy and refine optimumdosing.

Example 42

[0754] Human Clinical Trial: Monotherapy with Human Anti-151P3D4Antibody

[0755] Anti-151P3D4 antibodies are safe in connection with theabove-discussed adjunctive trial, a Phase II human clinical trialconfirms the efficacy and optimum dosing for monotherapy. Such trial isaccomplished, and entails the same safety and outcome analyses, to theabove-described adjunctive trial with the exception being that patientsdo not receive chemotherapy concurrently with the receipt of doses ofanti-151P3D4 antibodies.

Example 43

[0756] Human Clinical Trial: Diagnostic Imaging with Anti-151P3D4Antibody

[0757] Once again, as the adjunctive therapy discussed above is safewithin the safety criteria discussed above, a human clinical trial isconducted concerning the use of anti-151P3D4 antibodies as a diagnosticimaging agent. The protocol is designed in a substantially similarmanner to those described in the art, such as in Divgi et al. J. Natl.Cancer Inst. 83:97-104 (1991). The antibodies are found to be both safeand efficacious when used as a diagnostic modality.

Example 44

[0758] Homology Comparison of 151P3D4 to Known Sequences

[0759] Two variants of 151P3D4 have been identified, 151P3D4 v.1 and v2. The 151P3D4 v.1 gene exhibits strong homology to a previously clonedgene, namely the human cartilage linking protein 1 (gi 4503053), andshows 100% identity to that gene over the entire length of the protein(FIG. 4B). In addition, the 151P3D4 v.1 protein shows homology to thebovine and rat homologs of the human cartilage linking protein (gi1709660 and gi 9506519) (FIGS. 4F and 4G). 151P3D4 v.1 is a 354 aaprotein which localizes primarily to the extracellular compartment (seeTable XXI). The second variant, 151P3D4 v.2, is a 721 aa protein, thatshares identity with 151P3D4 v.1 over 200 amino acids (Table LV and FIG.4D). The 151P3D4 v.2 gene also exhibits homology to the human cartilagelink protein-1 (gi 4503053), showing 99% identity and 99% homology tothat protein (FIG. 4H). However, this homology between variant 2 andcartilage link protein does not extend over the entire length of variant2, but is limited to the last 400 aa of that protein. The first 400 aaof 151P3D4 v.2 show homology to human ribosomal protein L13a of the 60Ssubunit (gi. 18574549) (see Table XXI). Besides the addition of 400 aaat its N-terminus, 151P3D4 v.2 also differs from variant 1 in itslocalization profile. 151P3D4 v.2 localizes to the cytosol, withpotential localization to the nucleus (see Table XXI). Motif analysisrevealed the presence of link motif as well as immunoglobulin domain inboth 151P3D4 variants (see Table XXI).

[0760] Cartilage link protein-1, a protein with a known link motif, hasbeen shown to regulate tissue remodeling, bone resorption and proteininteraction (Chen Q et al. Dev Biol. 1995, 172:293). The importance ofcartilage link protein 1 is illustrated in engineered mice lackingcartilage link protein (Watanabe H, Yamada Y. Nat Genet. 1999, 21:225).These mutant mice demonstrate defects in cartilage and bone development.The cartilage link protein, via its link motif, mediates cell adhesionof fibroblasts and other cells to extracellular matrix (Yang B et al,Matrix Biol. 1998, 16:541). The link motif is a binding domain forhyaluronic acid (Kohda D et al, Cell. 1996, 86:767), with a structurevery similar to type C-lectin. It plays a role in the assembly ofextracellular matrix, cell adhesion, and migration (Kohda D et al, Cell.1996, 86:767). The immunoglobulin domain is a 100 aa long motif whichincludes a conserved intra-domain disulfide bond. Immunoglobulin-likedomains participate in protein interactions (Wang J, Springer T A.Immunol Rev. 1998, 163:197).

[0761] The presence of an immunoglobulin motif and a link motif indicatethat 151P3D4 regulates protein interactions and participates in theprocess of cell adhesion, cell migration, tumor formation andprogression. By way of its protein interaction domain, 151P3D4 functionsin regulating signal transduction in mammalian cells, thereby regulatinggene expression and cellular outcomes, including cell proliferation,survival, invasion, motility, etc, all of which have a direct effect ontumor growth and progression.

[0762] Accordingly, when 151P3D4 functions as a regulator of proteininteractions, cell adhesion, tumor formation, invasion or cellsignaling, 151P3D4 is used for therapeutic, diagnostic, prognosticand/or preventative purposes. In addition, when a variant of 151P3D4 isexpressed in cancerous tissues, such as those listed in Table I, theyare used for therapeutic, diagnostic, prognostic and/or preventativepurposes.

Example 45

[0763] Regulation of Transcription

[0764] The localization of 151P3D4 coupled to the presence of proteininteraction domains within its sequence, indicate that 151P3D4 modulatesthe transcriptional regulation of eukaryotic genes. Regulation of geneexpression is confirmed, e.g., by studying gene expression in cellsexpressing or lacking 151P3D4. For this purpose, two types ofexperiments are performed.

[0765] In the first set of experiments, RNA from parental and151P3D4-expressing cells are extracted and hybridized to commerciallyavailable gene arrays (Clontech) (Smid-Koopman E et al. Br J Cancer.2000. 83:246). Resting cells as well as cells treated with FBS, androgenor growth factors are compared. Differentially expressed genes areidentified in accordance with procedures known in the art. Thedifferentially expressed genes are then mapped to biological pathways(Chen K et al. Thyroid. 2001. 11:41.).

[0766] In the second set of experiments, specific transcriptionalpathway activation is evaluated using commercially available(Stratagene) luciferase reporter constructs including: NFkB-luc,SRE-luc, ELK1-luc, ARE-luc, p53-luc, and CRE-luc. These transcriptionalreporters contain consensus binding sites for known transcriptionfactors that lie downstream of well-characterized signal transductionpathways, and represent a good tool to ascertain pathway activation andscreen for positive and negative modulators of pathway activation.

[0767] Thus, 151P3D4 plays a role in gene regulation, and it is used asa target for diagnostic, prognostic, preventative and/or therapeuticpurposes.

Example 46

[0768] Identification and Confirmation of Potential Signal TransductionPathways

[0769] Many mammalian proteins have been reported to interact withsignaling molecules and to participate in regulating signaling pathways.(J Neurochem. 2001; 76:217-223). In particular, protein interactionmotifs have been instrumental in inducing kinase activation, recruitmentof proteins and complex formation (Samelson L. Annu Rev Immunol.2002;20:371). Based on the presence of a protein interacton motif,151P3D4 regulates signaling pathways important for cell growth andinvasion. In addition, the 151P3D4 protein contains severalphosphorylation sites (see Table XX) indicating an association withspecific signaling cascades. Using immunoprecipitation and Westernblotting techniques, proteins are identified that associate with 151P3D4and mediate signaling events. Several pathways known to play a role incancer biology can be regulated by 151P3D4, including phospholipidpathways such as PI3K, AKT, etc, adhesion and migration pathways,including FAK, Rho, Rac-1, β-catenin, etc, as well as mitogenic/survivalcascades such as ERK, p38, etc (Cell Growth Differ. 2000,11:279; J BiolChem. 1999, 274:801; Oncogene. 2000, 19:3003, J. Cell Biol. 1997,138:913.).

[0770] To confirm that 151P3D4 directly or indirectly activates knownsignal transduction pathways in cells, luciferase (luc) basedtranscriptional reporter assays are carried out in cells expressingindividual genes. These transcriptional reporters containconsensus-binding sites for known transcription factors that liedownstream of well-characterized signal transduction pathways. Thereporters and examples of these associated transcription factors, signaltransduction pathways, and activation stimuli are listed below.

[0771] 1. NFkB-luc, NFkB/Re1; Ik-kinase/SAPK; growth/apoptosis/stress

[0772] 2. SRE-luc, SRF/TCF/ELK1; MAPK/SAPK; growth/differentiation

[0773] 3. AP-1-luc, FOS/JUN; MAPK/SAPK/PKC; growth/apoptosis/stress

[0774] 4. ARE-luc, androgen receptor; steroids/MAPK;growth/differentiation/apoptosis

[0775] 5. p53-luc, p53; SAPK; growth/differentiation/apoptosis

[0776] 6. CRE-luc, CREB/ATF2; PKA/p38; growth/apoptosis/stress

[0777] 7. TCF-luc, TCF/Lef; β-catenin, Adhesion/invasion

[0778] Gene-mediated effects can be assayed in cells showing mRNAexpression. Luciferase reporter plasmids can be introduced bylipid-mediated transfection (TFX-50, Promega). Luciferase activity, anindicator of relative transcriptional activity, is measured byincubation of cell extracts with luciferin substrate and luminescence ofthe reaction is monitored in a luminometer.

[0779] Signaling pathways activated by 151P3D4 are mapped and used forthe identification and validation of therapeutic targets. When 151P3D4is involved in cell signaling, it is used as target for diagnostic,prognostic, preventative and/or therapeutic purposes.

Example 47

[0780] Involvement in Tumor Progression

[0781] Based on the role of link motif in cell adhesion, cell migrationand tumor formation, the 151P3D4 gene can contribute to tumor initiationand progression. The role of 151P3D4 in tumor growth is confirmed in avariety of primary and transfected cell lines including bladder, kidneyand ovary cell lines, as well as NIH 3T3 cells engineered to stablyexpress 151P3D4. Parental cells lacking 151P3D4 and cells expressing151P3D4 are evaluated for cell growth using a well-documentedproliferation assay (Fraser S P, Grimes J A, Djamgoz M B. Prostate.2000;44:61, Johnson D E, Ochieng J, Evans S L. Anticancer Drugs. 1996,7:288).

[0782] To confirm the role of 151P3D4 in the transformation process, itseffect in colony forming assays is investigated. Parental NIH-3T3 cellslacking 151P3D4 are compared to NIH-3T3 cells expressing 151P3D4, usinga soft agar assay under stringent and more permissive conditions (SongZ. et al. Cancer Res. 2000;60:6730).

[0783] To confirm the role of 151P3D4 in invasion and metastasis ofcancer cells, a well-established assay is used, e.g., a Transwell InsertSystem assay (Becton Dickinson) (Cancer Res. 1999; 59:6010). Controlcells, including bladder, ovary and kidney cell lines lacking 151P3D4are compared to cells expressing 151P3D4. Cells are loaded with thefluorescent dye, calcein, and plated in the top well of the Transwellinsert coated with a basement membrane analog. Invasion is determined byfluorescence of cells in the lower chamber relative to the fluorescenceof the entire cell population.

[0784] 151P3D4 can also play a role in cell cycle and apoptosis.Parental cells and cells expressing 151P3D4 are compared for differencesin cell cycle regulation using a well-established BrdU assay(Abdel-Malek Z A. J Cell Physiol. 1988, 136:247). In short, cells aregrown under both optimal (full serum) and limiting (low serum)conditions are labeled with BrdU and stained with anti-BrdU Ab andpropidium iodide. Cells are analyzed for entry into the G1, S, and G2Mphases of the cell cycle. Alternatively, the effect of stress onapoptosis is evaluated in control parental cells and cells expressing151P3D4, including normal and tumor bladder, kidney and ovary cells.Engineered and parental cells are treated with various chemotherapeuticagents, such as etoposide, taxol, etc, and protein synthesis inhibitors,such as cycloheximide. Cells are stained with annexin V-FITC and celldeath is measured by FACS analysis. The modulation of cell death by151P3D4 can play a critical role in regulating tumor progression andtumor load.

[0785] When 151P3D4 plays a role in cell growth, transformation,invasion or apoptosis, it is used as a target for diagnostic,prognostic, preventative and/or therapeutic purposes.

Example 48

[0786] Involvement in Angiogenesis

[0787] Angiogenesis or new capillary blood vessel formation is necessaryfor tumor growth (Hanahan D, Folkman J. Cell. 1996, 86:353; Folkman J.Endocrinology. 1998 139:441). Based on the effect of phsophodieseteraseinhibitors on endothelial cells, 151P3D4 plays a role in angiogenesis(DeFouw L et al, Microvasc Res 2001, 62:263). Several assays have beendeveloped to measure angiogenesis in vitro and in vivo, such as thetissue culture assays endothelial cell tube formation and endothelialcell proliferation. Using these assays as well as in vitroneo-vascularization, the role of 151P3D4 in angiogenesis, enhancement orinhibition, is confirmed.

[0788] For example, endothelial cells engineered to express 151P3D4 areevaluated using tube formation and proliferation assays. The effect of151P3D4 is also confirmed in animal models in vivo. For example, cellseither expressing or lacking 151P3D4 are implanted subcutaneously inimmunocompromised mice. Endothelial cell migration and angiogenesis areevaluated 5-15 days later using immunohistochemistry techniques. 151P3D4affects angiogenesis, and it is used as a target for diagnostic,prognostic, preventative and/or therapeutic purposes

Example 49

[0789] Involvement in Protein-Protein Interactions

[0790] Link as well as immunoglobulin motifs have been shown to mediateinteraction with other proteins, resulting in the formation of amulti-protein complex ( ). Using immunoprecipitation techniques as wellas two yeast hybrid systems, proteins are identified that associate with151P3D4. Immunoprecipitates from cells expressing 151P3D4 and cellslacking 151P3D4 are compared for specific protein-protein associations.

[0791] Studies are performed to confirm the extent of association of151P3D4 with effector molecules, such as nuclear proteins, transcriptionfactors, kinases, phsophates etc. Studies comparing 151P3D4 positive and151P3D4 negative cells as well as studies comparing unstimulated/restingcells and cells treated with epithelial cell activators, such ascytokines, growth factors and anti-integrin Ab reveal uniqueinteractions.

[0792] In addition, protein-protein interactions are confirmed using twoyeast hybrid methodology (Curr Opin Chem Biol. 1999, 3:64). A vectorcarrying a library of proteins fused to the activation domain of atranscription factor is introduced into yeast expressing a151P3D4-DNA-binding domain fusion protein and a reporter construct.Protein-protein interaction is detected by calorimetric reporteractivity. Specific association with effector molecules and transcriptionfactors directs one of skill to the mode of action of 151P3D4, and thusidentifies therapeutic, prognostic, preventative and/or diagnostictargets for cancer. This and similar assays are also used to identifyand screen for small molecules that interact with 151P3D4.

[0793] Thus it is found that 151P3D4 associates with proteins and smallmolecules. Accordingly, 151P3D4 and these proteins and small moleculesare used for diagnostic, prognostic, preventative and/or therapeuticpurposes.

Example 50

[0794] Involvement in Adhesion

[0795] Cell adhesion plays a critical role in tissue colonization andmetastasis. The presence of link motif in 151P3D4 is indicative of itsrole in cell adhesion. To confirm that 151P3D4 plays a role in celladhes control cells lacking 151P3D4 are compared to cells expressing151P3D4, using techniques previously described (see, e.g., Haier et al,Br. J. Cancer. 1999, 80:1867; Lehr and Pienta, J. Natl. Cancer Inst.1998, 90:118). Briefly, in one embodiment, cells labeled with afluorescent indicator, such as calcein, are incubated on tissue culturewells coated with media alone or with matrix proteins. Adherent cellsare detected by fluorimetric analysis and percent adhesion iscalculated. This experimental system can be used to identify proteins,antibodies and/or small molecules that modulate cell adhesion toextracellular matrix and cell-cell interaction. Since cell adhesionplays a critical role in tumor growth, progression, and, colonization,the gene involved in this process can serves as a diagnostic,preventative and therapeutic modality.

[0796] Throughout this application, various website data content,publications, patent applications and patents are referenced. (Websitesare referenced by their Uniform Resource Locator, or URL, addresses onthe World Wide Web.) The disclosures of each of these references arehereby incorporated by reference herein in their entireties.

[0797] The present invention is not to be limited in scope by theembodiments disclosed herein, which are intended as single illustrationsof individual aspects of the invention, and any that are functionallyequivalent are within the scope of the invention. Various modificationsto the models and methods of the invention, in addition to thosedescribed herein, will become apparent to those skilled in the art fromthe foregoing description and teachings, and are similarly intended tofall within the scope of the invention. Such modifications or otherembodiments can be practiced without departing from the true scope andspirit of the invention. TABLE I Tissues that Express 151P3D4 WhenMalignant Bladder Kidney Colon Lung Ovary Breast Stomach Uterus

[0798] TABLE II Amino Acid Abbreviations SINGLE LETTER THREE LETTER FULLNAME F Phe phenylalanine L Leu leucine S Ser serine Y Tyr tyrosine C Cyscysteine W Trp tryptophan P Pro proline H His histidine Q Gln glutamineR Arg arginine I Ile isoleucine M Met methionine T Thr threonine N Asnasparagine K Lys lysine V Val valine A Ala alanine D Asp aspartic acid EGlu glutamic acid G Gly glycine

[0799] TABLE III Amino Acid Substitution Matrix A C D E F G H I K L M NP Q R S T V W Y . 4 0 −2 −1 −2 0 −2 −1 −1 −1 −1 −2 −1 −1 −1 1 0 0 −3 −2A 9 −3 −4 −2 −3 −3 −1 −3 −1 −1 −3 −3 −3 −3 −1 −1 −1 −2 −2 C 6 2 −3 −1 −1−3 −1 −4 −3 1 −1 0 −2 0 −1 −3 −4 −3 D 5 −3 −2 0 −3 1 −3 −2 0 −1 2 0 0 −1−2 −3 −2 E 6 −3 −1 0 −3 0 0 −3 −4 −3 −3 −2 −2 −1 1 3 F 6 −2 −4 −2 −4 −30 −2 −2 −2 0 −2 −3 −2 −3 G 8 −3 −1 −3 −2 1 −2 0 0 −1 −2 −3 −2 2 H 4 −3 21 −3 −3 −3 −3 −2 −1 3 −3 −1 I 5 −2 −1 0 −1 1 2 0 −1 −2 −3 −2 K 4 2 −3 −3−2 −2 −2 −1 1 −2 −1 L 5 −2 −2 0 −1 −1 −1 1 −1 −1 M 6 −2 0 0 1 0 −3 −4 −2N 7 −1 −2 −1 −1 −2 −4 −3 P 5 1 0 −1 −2 −2 −1 Q 5 −1 −1 −3 −3 −2 R 4 1 −2−3 −2 S 5 0 −2 −2 T 4 −3 −1 V 11 2 W 7 Y

[0800] TABLE IV (A) HLA Class I Supermotifs/Motifs POSITION POSITIONPOSITION 3 (Primary C Terminus (Primary 2 (Primary Anchor) Anchor)Anchor) SUPER- MOTIFS A1 TI LVMS FWY A2 LIVM ATQ IV MATL A3 VSMA TLI RKA24 YF WIVLMT FI YWLM B7 P VILF MWYA B27 RHK FYL WMIVA B44 E D FWYLIMVAB58 ATS FWY LIVMA B62 QL IVMP FWYMIVLA MOTIFS A1 TSM Y A1 DE AS Y A2.1LM VQIAT V LIMAT A3 LMVISATF CGD KYR HFA A11 VTMLISAGN CDF K RYH A24 YFWM FLIW A*3101 MVT ALIS R K A*3301 MVALF IST RK A*6801 AVT MSLI RKB*0702 P LMF WYAIV B*3501 P LMFWY IVA B51 P LIVF WYAM B*5301 P IMFWY ALVB*5401 P ATIV LMFWY

[0801] TABLE IV (B) HLA Class II Supermotif 1 6 9 W, F, Y, V, .I, L A,V, I, L, P, C, S, T A, V, I, L, C, S, T, M, Y

[0802] TABLE IV (C) HLA Class II Motifs MOTIFS 1° anchor 1 2 3 4 5 1°anchor 6 7 8 9 DR4 preferred FMYLIVW M T I VSTCPALIM MH MH deleterious WR WDE DR1 preferred MFLIVWY PAMQ VMATSPLIC M AVM deleterious C CH FD CWDGDE D DR7 preferred MFLIVWY M W A IVMSACTPL M IV deleterious C G GRD N GDR3 MOTIFS 1° anchor 1 2 3 1° anchor 4 5 1° anchor 6 motif LIVMFY D apreferred motif LIVMFAY DNQEST KRH b preferred DR MFLIVWY VMSTACPLISupermotif

[0803] TABLE IV (D) HLA Class I Supermotifs SUPER- MOTIFS POSITION: 1 23 4 5 6 7 8 C-terminus A1 $\frac{1{^\circ}\quad {Anchor}}{TILVMS}$

$\frac{1{^\circ}\quad {Anchor}}{FWY}$

A2 $\frac{1{^\circ}\quad {Anchor}}{LIVMATQ}$

$\frac{1{^\circ}\quad {Anchor}}{LIVMAT}$

A3 preferred $\frac{1{^\circ}\quad {Anchor}}{VSMATLI}$

YFW (4/5) YFW (3/5) YFW (4/5) P (4/5)$\frac{1{^\circ}\quad {Anchor}}{RK}$

deleterious DE (3/5); DE P (5/5) (4/5) A24$\frac{1{^\circ}\quad {Anchor}}{YFWIVLMT}$

$\frac{1{^\circ}\quad {Anchor}}{FIYWLM}$

B7 preferred FWY (5/5) LIVM (3/5) $\frac{1{^\circ}\quad {Anchor}}{P}$

FWY (4/5) FWY (3/5) $\frac{1{^\circ}\quad {Anchor}}{VILFMWYA}$

deleterious DE (3/5); DE G QN DE P(5/5); (3/5) (4/5) (4/5) (4/5) G(4/5);A(3/5); QN(3/5) B27 $\frac{1{^\circ}\quad {Anchor}}{RHK}$

$\frac{1{^\circ}\quad {Anchor}}{FYLWMIVA}$

B44 $\frac{1{^\circ}\quad {Anchor}}{ED}$

$\frac{1{^\circ}\quad {Anchor}}{FWYLIMVA}$

B58 $\frac{1{^\circ}\quad {Anchor}}{ATS}$

$\frac{1{^\circ}\quad {Anchor}}{FWYLIVMA}$

B62 $\frac{1{^\circ}\quad {Anchor}}{QLIVMP}$

$\frac{1{^\circ}\quad {Anchor}}{FWYMIVLA}$

[0804] TABLE IV (E): HLA Class I Motifs POSITION: 1 2 3 4 5 6 7 8 9C-terminus A1 9-mer preferred deleterious GFYW DE

DEA RHKLIVMP YFW A G P A DEQN YFW

A1 9-mer preferred deleterious GRHK A ASTCLIVM RHKDEPYFW

GSTC DE PQN ASTC RHK LIVM PG DE GP

A1 10-mer preferred deleterious YFW GP

DEAQN RHKGLIVM A DE YFWQN RHK QNA PASTC RHKYFW GDE RHK P A

A1 10-mer preferred deleterious YFW RHK STCLIVM RHKDEPYFW

A YFW P G PG G PRHK YFW QN

A2.1 9-mer preferred deleterious YFW DEP

YFW DERKH STC YFW RKH A DERKH P

A2.1 10-mer preferred deleterious AYFW DEP

LVIM DE G RKHA P G RKH FYWLVIM DERKH RKH

A3 preferred deleterious RHK DEP

YFW DE PRHKYFW A YFW P

A11 preferred deleterious A DEP

YFW YFW A YFW YFW A P G

A24 9-mer preferred deleterious YFWRHK DEG

DE STC G QNP DERHK YFW G YFW AQN

A24 10-mer preferred deleterious

GDE P QN YFWP RHK DE P A QN DEA

A3101 preferred deleterious RHK DEP

YFW DE P ADE YFW DE YFW DE AP DE

A3301 preferred deleterious GP

YFW DE AYFW

A6801 preferred deleterious YFWSTC GP

DEG YFWLIVM RHK YFW P A

B0702 preferred deleterious RHKFWY DEQNP

RHK DEP DE RHK DE RHK GDE RHK QN PA DE

B3501 preferred deleterious FWYLIVM AGP

FWY G G FWY

B51 preferred deleterious LIVMFWY AGPDERHKSTC

FWY STC FWY DE G G DEQN FWY GDE

B5301 preferred deleterious LIVMFWY AGPQN

FWY STC FWY G LIVMFWY RHKQN FWY DE

B5401 preferred deleterious FWY GPQNDE

FWYLIVM GDESTC LIVM RHKDE DE ALIVM QNDGE FWYAP DE

[0805] TABLE V Pos 1 2 3 4 5 6 7 8 9 Score SeqID v.1-A1-9mers: 151P3D4126 I T D L T L E D Y 62.500 264 L I H P T K L T Y 25.000 14 W A D H L SD N Y 25.000 130 T L E D Y G R Y K 18.000 57 V T L P C K F Y R 12.500280 L N D G A Q I A K 12.500 230 N T V P G V R N Y 12.500 153 A L D L QG V V F 10.000 18 L S D N Y T L D H 3.750 293 F A A W K I L G Y 2.500155 D L Q G V V F P Y 2.500 144 G L E D D T V V V 1.800 43 E A E Q A K VF S 1.800 41 L V E A E Q A K V 1.800 213 G S V Q Y P I T K 1.500 183 D QD A V I A S F 1.500 119 D S D A S L V I T 1.500 64 Y R D P T A F G S1.250 129 L T L E D Y G R Y 1.250 201 G L D W C N A G W 1.000 181 C L DQ D A V I A 1.000 23 T L D H D R A I H 1.000 209 W L S D G S V Q Y 1.000308 W L A D G S V R Y 1.000 68 T A F G S G I H K 1.000 33 Q A E N G P HL L 0.900 141 V I E G L E D D T 0.900 254 T S N F N G R F Y 0.750 117 GS D S D A S L V 0.750 255 S N F N G R F Y Y 0.625 337 F P D K K H K L Y0.625 56 N V T L P C K F Y 0.500 335 V G F P D K K H K 0.500 187 V I A SF D Q L Y 0.500 158 G V V F P Y F P R 0.500 91 E V D V F V S M G 0.500325 C S P T E A A V R 0.300 253 F T S N F N G R F 0.250 103 K T Y G G YQ G R 0.250 303 R C D A G W L A D 0.250 97 S M G Y H K K T Y 0.250 327 PT E A A V R F V 0.225 89 L K E V D V F V S 0.225 159 V V F P Y F P R L0.200 95 F V S M G Y H K K 0.200 128 D L T L E D Y G R 0.200 324 R C S PT E A A V 0.200 40 L L V E A E Q A K 0.200 329 E A A V R F V G F 0.200215 V Q Y P I T K P R 0.150 240 F W D K D K S R Y 0.125 92 V D V F V S MG Y 0.125 161 F P Y F P R L G R 0.125 247 R Y D V F C F T S 0.125 148 DT V V V A L D L 0.125 345 Y G V Y C F R A Y 0.125 343 K L Y G V Y C F R0.100 54 G G N V T L P C K 0.100 249 D V F C F T S N F 0.100 289 V G Q IF A A W K 0.100 272 Y D E A V Q A C L 0.090 174 F H E A Q Q A C L 0.090138 K C E V I E G L E 0.090 312 G S V R Y P I S R 0.075 245 K S R Y D VF C F 0.075 210 L S D G S V Q Y P 0.075 71 G S G I H K I R I 0.075 85 TS D Y L K E V D 0.075 314 V R Y P I S R P R 0.050 219 I T K P R E P C G0.050 4 L L L L V L I S I 0.050 309 L A D G S V R Y P 0.050 185 D A V IA S F D Q 0.050 176 E A Q Q A C L D Q 0.050 146 E D D T V V V A L 0.050270 L T Y D E A V Q A 0.050 166 R L G R Y N L N F 0.050 150 V V V A L DL Q G 0.050 107 G Y Q G R V F L K 0.050 6 L L V L I S I C W 0.050 3 S LL L L V L I S 0.050 326 S P T E A A V R F 0.050 72 S G I H K I R I K0.050 123 S L V I T D L T L 0.050 145 L E D D T V V V A 0.050 251 F C FT S N F N G 0.050 232 V P G V R N Y G F 0.050 131 L E D Y G R Y K C0.050 222 P R E P C G G Q N 0.045 156 L Q G V V F P Y F 0.030 189 A S FD Q L Y D A 0.030 2 K S L L L L V L I 0.030 162 P Y F P R L G R Y 0.025316 Y P I S R P R R R 0.025 55 G N V T L P C K F 0.025 190 S F D Q L Y DA W 0.025 105 Y G G Y Q G R V F 0.025 70 F G S G I H K I R 0.025 271 T YD E A V Q A C 0.025 194 L Y D A W R G G L 0.025 v.2-A1-9mers: 151P3D4 34K V D L L V P T K 20.000 385 S L E E G L G G K 18.000 183 T L E E K R KE K 18.000 123 N T N P S R R P Y 12.500 1 M L E H T T K T F 9.000 97 S CE G I N I S G 4.500 59 F V G S Y K L A Y 2.500 367 P A D L A G S G Y2.500 220 Y T E S P G G G S 2.250 238 T I A P L A A T R 2.000 208 Q A EK N M K K K 1.800 157 A S E A Y K K V C 1.350 354 K S E N N S W Y V1.350 226 G G S P R G L G F 1.250 302 S T Y D S L S P Y 1.250 188 R K EK A E I H Y 1.125 400 K A E N G P H L L 0.900 191 K A E I H Y R K N0.900 17 V V E S I R D H S 0.900 382 A I E S L E E G L 0.900 51 A K D FG H V Q F 0.500 7 K T F P L R A L H 0.500 134 Q V P S R I F W R 0.500296 S C P T S S S T Y 0.500 70 D G E H W T V Y Q 0.450 105 G S F C R N KL K 0.300 103 I S G S F C R N K 0.300 373 S G Y C G A L W K 0.250 180 VT A T L E E K R 0.250 37 L L V P T K V T G 0.200 389 G L G G K Q K D K0.200 168 G A P H E V G W K 0.200 181 T A T L E E K R K 0.200 179 A V TA T L E E K 0.200 56 H V Q F V G S Y K 0.200 306 S L S P Y G P R N 0.200361 Y V E N G R P A D 0.180 323 P S G G G G L K K 0.150 207 K Q A E K NM K K 0.150 222 E S P G G G S P R 0.150 295 S S C P T S S S T 0.150 305D S L S P Y G P R 0.150 83 R K D K V L L G R 0.125 68 S N D G E H W T V0.125 101 I N I S G S F C R 0.125 169 A P H E V G W K Y 0.125 46 I I T QG A K D F 0.100 150 S C C P Q G H A S 0.100 154 Q G H A S E A Y K 0.10075 T V Y Q D E K Q R 0.100 78 Q D E K Q R K D K 0.090 384 E S L E E G LG G 0.075 133 F Q V P S R I F W 0.075 279 A S P A A W L P L 0.075 4 H TT K T F P L R 0.050 145 K A D G G S C C P 0.050 95 V V S C E G I N I0.050 280 S P A A W L P L R 0.050 346 R G K P Q R K P K 0.050 265 H R PP A L S A R 0.050 377 G A L W K A I E S 0.050 44 T G I I T Q G A K 0.050326 G G G L K K P A R 0.050 288 R T P W T R P S S 0.050 322 S P S G G GG L K 0.050 237 K T I A P L A A T 0.050 167 S G A P H E V G W 0.050 112L K Y L A F L H K 0.050 121 R M N T N P S R R 0.050 303 T Y D S L S P YG 0.050 199 N K Q L M R L Q K 0.050 386 L E E G L G G K Q 0.045 372 G SG Y C G A L W 0.030 261 G S S A H R P P A 0.030 262 S S A H R P P A L0.030 69 N D G E H W T V Y 0.025 74 W T V Y Q D E K Q 0.025 21 I R D H SG Q K M 0.025 314 N P L P N P R H S 0.025 291 W T R P S S C P T 0.025 99E G I N I S G S F 0.025 43 V T G I I T Q G A 0.025 316 L P N P R H S P S0.025 47 I T Q G A K D F G 0.025 55 G H V Q F V G S Y 0.025 274 A P V PA A S P A 0.025 211 K N M K K K I D K 0.025 284 W L P L R T P W T 0.020241 P L A A T R A T R 0.020 190 E K A E I H Y R K 0.020 344 L A R G K PQ R K 0.020 20 S I R D H S G Q K 0.020 163 K V C L S G A P H 0.020 155 GH A S E A Y K K 0.020 369 D L A G S G Y C G 0.020 87 V L L G R K A V V0.020 343 V L A R G K P Q R 0.020 12 R A L H I V V E S 0.020 203 M R L QK Q A E K 0.020 358 N S W Y V E N G R 0.015

[0806] TABLE VI Pos 1 2 3 4 5 6 7 8 9 0 Score SeqID v.1-A1-10mers:151P3D4 91 E V D V F V S M G Y 125.000 41 L V E A E Q A K V F 9.000 33 QA E N G P H L L V 4.500 43 E A E Q A K V F S H 4.500 254 T S N F N G R FY Y 3.750 117 G S D S D A S L V I 3.750 181 C L D Q D A V I A S 2.500 23T L D H D R A I H I 2.500 263 Y L I H P T K L T Y 2.500 324 R C S P T EA A V R 2.000 130 T L E D Y G R Y K C 1.800 144 G L E D D T V V V A1.800 85 T S D Y L K E V D V 1.500 210 L S D G S V Q Y P I 1.500 126 I TD L T L E D Y G 1.250 253 F T S N F N G R F Y 1.250 327 P T E A A V R FV G 1.125 303 R C D A G W L A D G 1.000 279 C L N D G A Q I A K 1.000309 L A D G S V R Y P I 1.000 141 V I E G L E D D T V 0.900 96 V S M G YH K K T Y 0.750 190 S F D Q L Y D A W R 0.500 125 V I T D L T L E D Y0.500 201 G L D W C N A G W L 0.500 56 N V T L P C K F Y R 0.500 128 D LT L E D Y G R Y 0.500 14 W A D H L S D N Y T 0.500 129 L T L E D Y G R YK 0.500 186 A V I A S F D Q L Y 0.500 138 K C E V I E G L E D 0.450 93 DV F V S M G Y H K 0.400 288 K V G Q I F A A W K 0.400 119 D S D A S L VI T D 0.375 71 G S G I H K I R I K 0.300 325 C S P T E A A V R F 0.300106 G G Y Q G R V F L K 0.250 64 Y R D P T A F G S G 0.250 67 P T A F GS G I H K 0.250 280 L N D G A Q I A K V 0.250 230 N T V P G V R N Y G0.250 212 D G S V Q Y P I T K 0.250 39 H L L V E A E Q A K 0.200 155 D LQ G V V F P Y F 0.200 334 F V G F P D K K H K 0.200 231 T V P G V R N YG F 0.200 152 V A L D L Q G V V F 0.200 154 L D L Q G V V F P Y 0.125292 I F A A W K I L G Y 0.125 161 F P Y F P R L G R Y 0.125 55 G N V T LP C K F Y 0.125 157 Q G V V F P Y F P R 0.125 229 Q N T V P G V R N Y0.125 311 D G S V R Y P I S R 0.125 81 W T K L T S D Y L K 0.100 53 R GG N V T L P C K 0.100 314 V R Y P I S R P R R 0.100 214 S V Q Y P I T KP R 0.100 251 F C F T S N F N G R 0.100 159 V V F P Y F P R L G 0.100153 A L D L Q G V V F P 0.100 89 L K E V D V F V S M 0.090 18 L S D N YT L D H D 0.075 2 K S L L L L V L I S 0.075 122 A S L V I T D L T L0.075 337 F P D K K H K L Y G 0.062 291 Q I F A A W K I L G 0.050 22 Y TL D H D R A I H 0.050 236 R N Y G F W D K D K 0.050 145 L E D D T V V VA L 0.050 149 T V V V A L D L Q G 0.050 35 E N G P H L L V E A 0.050 57V T L P C K F Y R D 0.050 343 K L Y G V Y C F R A 0.050 208 G W L S D GS V Q Y 0.050 3 S L L L L V L I S I 0.050 17 H L S D N Y T L D H 0.050271 T Y D E A V Q A C L 0.050 307 G W L A D G S V R Y 0.050 5 L L L V LI S I C W 0.050 222 P R E P C G G Q N T 0.045 272 Y D E A V Q A C L N0.045 331 A V R F V G F P D K 0.040 247 R Y D V F C F T S N 0.025 13 C WA D H L S D N Y 0.025 242 D K D K S R Y D V F 0.025 219 I T K P R E P CG G 0.025 160 V F P Y F P R L G R 0.025 238 Y G F W D K D K S R 0.025103 K T Y G G Y Q G R V 0.025 344 L Y G V Y C F R A Y 0.025 335 V G F PD K K H K L 0.025 270 L T Y D E A V Q A C 0.025 54 G G N V T L P C K F0.025 148 D T V V V A L D L Q 0.025 336 G F P D K K H K L Y 0.025 227 GG Q N T V P G V R 0.025 31 H I Q A E N G P H L 0.020 40 L L V E A E Q AK V 0.020 269 K L T Y D E A V Q A 0.020 v.2-A1-10mers: 151P3D4 191 K A EI H Y R K N K 18.000 295 S S C P T S S S T Y 7.500 68 S N D G E H W T VY 6.250 400 K A E N G P H L L V 4.500 105 G S F C R N K L K Y 3.750 157A S E A Y K K V C L 2.700 361 Y V E N G R P A D L 1.800 77 Y Q D E K Q RK D K 1.500 372 G S G Y C G A L W K 1.500 7 K T F P L R A L H I 1.250382 A I E S L E E G L G 0.900 385 S L E E G L G G K Q 0.900 386 L E E GL G G K Q K 0.900 183 T L E E K R K E K A 0.900 17 V V E S I R D H S G0.900 97 S C E G I N I S G S 0.900 133 F Q V P S R I F W R 0.750 301 S ST Y D S L S P Y 0.750 145 K A D G G S C C P Q 0.500 123 N T N P S R R PY H 0.500 182 A T L E E K R K E K 0.500 43 V T G I I T Q G A K 0.500 168G A P H E V G W K Y 0.500 34 K V D L L V P T K V 0.500 278 A A S P A A WL P L 0.500 100 G I N I S G S F C R 0.500 237 K T I A P L A A T R 0.500167 S G A P H E V G W K 0.500 21 I R D H S G Q K M K 0.500 180 V T A T LE E K R K 0.500 24 H S G Q K M K Q D K 0.300 321 H S P S G G G G L K0.300 384 E S L E E G L G G K 0.300 279 A S P A A W L P L R 0.300 354 KS E N N S W Y V E 0.270 74 W T V Y Q D E K Q R 0.250 322 S P S G G G G LK K 0.250 250 I G H P G G R T P R 0.250 220 Y T E S P G G G S P 0.225102 N I S G S F C R N K 0.200 75 T V Y Q D E K Q R K 0.200 342 N V L A RG K P Q R 0.200 178 Q A V T A T L E E K 0.200 47 I T Q G A K D F G H0.125 152 C P Q G H A S E A Y 0.125 122 M N T N P S R R P Y 0.125 58 Q FV G S Y K L A Y 0.125 366 R P A D L A G S G Y 0.125 225 G G G S P R G LG F 0.125 54 F G H V Q F V G S Y 0.125 238 T I A P L A A T R A 0.100 154Q G H A S E A Y K K 0.100 284 W L P L R T P W T R 0.100 45 G I I T Q G AK D F 0.100 13 A L H I V V E S I R 0.100 179 A V T A T L E E K R 0.10037 L L V P T K V T G I 0.100 111 K L K Y L A F L H K 0.100 1 M L E H T TK T F P 0.090 208 Q A E K N M K K K I 0.090 227 G S P R G L G F I F0.075 96 V S C E G I N I S G 0.075 240 A P L A A T R A T R 0.050 115 L AF L H K R M N T 0.050 104 S G S F C R N K L K 0.050 367 P A D L A G S GY C 0.050 206 Q K Q A E K N M K K 0.050 302 S T Y D S L S P Y G 0.050221 T E S P G G G S P R 0.050 129 R P Y H F Q V P S R 0.050 94 V V V S CE G I N I 0.050 291 W T R P S S C P T S 0.050 83 R K D K V L L G R K0.050 274 A P V P A A S P A A 0.050 216 K I D K Y T E S P G 0.050 388 EG L G G K Q K D K 0.050 325 G G G G L K K P A R 0.050 124 T N P S R R PY H F 0.050 316 L P N P R H S P S G 0.050 210 E K N M K K K I D K 0.05070 D G E H W T V Y Q D 0.045 188 R K E K A E I H Y R 0.045 30 K Q D K KV D L L V 0.037 19 E S I R D H S G Q K 0.030 305 D S L S P Y G P R N0.030 261 G S S A H R P P A L 0.030 262 S S A H R P P A L S 0.030 222 ES P G G G S P R G 0.030 207 K Q A E K N M K K K 0.030 166 L S G A P H EV G W 0.030 288 R T P W T R P S S C 0.025 198 K N K Q L M R L Q K 0.025228 S P R G L G F I F K 0.025 357 N N S W Y V E N G R 0.025 226 G G S PR G L G F I 0.025 51 A K D F G H V Q F V 0.025 247 A T R I G H P G G R0.025 202 L M R L Q K Q A E K 0.020 59 F V G S Y K L A Y S 0.020 33 K KV D L L V P T K 0.020

[0807] TABLE VII Pos 1 2 3 4 5 6 7 8 9 Score SeqID v.1-A2-9mers: 151P3D488 Y L K E V D V F V 252.512 4 L L L L V L I S I 150.931 7 L V L I S I CW A 34.588 263 Y L I H P T K L T 34.279 5 L L L V L I S I C 29.468 151 VV A L D L Q G V 23.795 159 V V F P Y F P R L 22.339 123 S L V I T D L TL 21.362 84 L T S D Y L K E V 15.486 32 I Q A E N G P H L 15.096 298 I LG Y D R C D A 8.446 279 C L N D G A Q I A 8.351 290 G Q I F A A W K I7.933 291 Q I F A A W K I L 7.575 144 G L E D D T V V V 7.483 90 K E V DV F V S M 2.634 106 G G Y Q G R V F L 2.454 2 K S L L L L V L I 2.028 22Y T L D H D R A I 2.022 257 F N G R F Y Y L I 1.786 186 A V I A S F D QL 1.740 270 L T Y D E A V Q A 1.539 209 W L S D G S V Q Y 1.405 308 W LA D G S V R Y 1.405 343 K L Y G V Y C F R 1.377 34 A E N G P H L L V1.352 76 K I R I K W T K L 1.328 152 V A L D L Q G V V 1.328 189 A S F DQ L Y D A 1.132 142 I E G L E D D T V 1.127 227 G G Q N T V P G V 1.044181 C L D Q D A V I A 0.815 41 L V E A E Q A K V 0.662 137 Y K C E V I EG L 0.631 116 G G S D S D A S L 0.572 178 Q Q A C L D Q D A 0.504 306 AG W L A D G S V 0.490 207 A G W L S D G S V 0.490 179 Q A C L D Q D A V0.473 324 R C S P T E A A V 0.454 346 G V Y C F R A Y N 0.436 180 A C LD Q D A V I 0.424 276 V Q A C L N D G A 0.420 193 Q L Y D A W R G G0.332 284 A Q I A K V G Q I 0.316 86 S D Y L K E V D V 0.309 39 H L L VE A E Q A 0.306 96 V S M G Y H K K T 0.306 202 L D W C N A G W L 0.299 3S L L L L V L I S 0.260 145 L E D D T V V V A 0.254 278 A C L N D G A QI 0.252 281 N D G A Q I A K V 0.222 143 E G L E D D T V V 0.212 172 L NF H E A Q Q A 0.204 8 V L I S I C W A D 0.190 117 G S D S D A S L V0.182 268 T K L T Y D E A V 0.175 256 N F N G R F Y Y L 0.155 223 R E PC G G Q N T 0.145 246 S R Y D V F C F T 0.142 156 L Q G V V F P Y F0.134 81 W T K L T S D Y L 0.129 6 L L V L I S I C W 0.127 10 I S I C WA D H L 0.116 40 L L V E A E Q A K 0.104 24 L D H D R A I H I 0.101 287A K V G Q I F A A 0.092 50 F S H R G G N V T 0.092 122 A S L V I T D L T0.088 83 K L T S D Y L K E 0.078 36 N G P H L L V E A 0.075 155 D L Q GV V F P Y 0.075 166 R L G R Y N L N F 0.075 71 G S G I H K I R I 0.068187 V I A S F D Q L Y 0.066 108 Y Q G R V F L K G 0.066 131 L E D Y G RY K C 0.066 336 G F P D K K H K L 0.061 255 S N F N G R F Y Y 0.057 15 AD H L S D N Y T 0.057 199 R G G L D W C N A 0.055 141 V I E G L E D D T0.055 97 S M G Y H K K T Y 0.054 121 D A S L V I T D L 0.051 262 Y Y L IH P T K L 0.050 164 F P R L G R Y N L 0.049 251 F C F T S N F N G 0.0481 M K S L L L L V L 0.048 288 K V G Q I F A A W 0.043 57 V T L P C K F YR 0.042 260 R F Y Y L I H P T 0.038 56 N V T L P C K F Y 0.036 231 T V PG V R N Y G 0.036 224 E P C G G Q N T V 0.034 53 R G G N V T L P C 0.032334 F V G F P D K K H 0.030 201 G L D W C N A G W 0.030 9 L I S I C W AD H 0.030 58 T L P C K F Y R D 0.028 v.2-A2-9mers: 151P3D4 378 A L W K AI E S L 199.826 284 W L P L R T P W T 188.536 87 V L L G R K A V V179.368 234 F I F K T I A P L 114.985 86 K V L L G R K A V 78.811 165 CL S G A P H E V 69.552 88 L L G R K A V V V 48.478 114 Y L A F L H K R M22.853 231 G L G F I F K T I 19.822 201 Q L M R L Q K Q A 18.382 52 K DF G H V Q F V 15.825 57 V Q F V G S Y K L 13.624 13 A L H I V V E S I11.758 230 R G L G F I F K T 9.124 9 F P L R A L H I V 7.287 67 Y S N DG E H W T 5.046 354 K S E N N S W Y V 4.195 100 G I N I S G S F C 3.75738 L V P T K V T G I 3.569 30 K Q D K K V D L L 3.417 95 V V S C E G I NI 1.552 110 N K L K Y L A F L 1.389 68 S N D G E H W T V 1.362 138 R I FW R Q E K A 1.238 336 C Q G Q K H N V L 0.888 36 D L L V P T K V T 0.848237 K T I A P L A A T 0.833 117 F L H K R M N T N 0.788 362 V E N G R PA D L 0.706 172 E V G W K Y Q A V 0.685 107 F C R N K L K Y L 0.617 35 VD L L V P T K V 0.608 81 K Q R K D K V L L 0.576 375 Y C G A L W K A I0.533 93 A V V V S C E G I 0.447 308 S P Y G P R N P L 0.446 158 S E A YK K V C L 0.415 27 Q K M K Q D K K V 0.357 175 W K Y Q A V T A T 0.35033 K K V D L L V P T 0.342 232 L G F I F K T I A 0.318 173 V G W K Y Q AV T 0.281 289 T P W T R P S S C 0.269 242 L A A T R A T R I 0.246 279 AS P A A W L P L 0.237 29 M K Q D K K V D L 0.207 156 H A S E A Y K K V0.202 133 F Q V P S R I F W 0.191 370 L A G S G Y C G A 0.176 262 S S AH R P P A L 0.139 104 S G S F C R N K L 0.139 249 R I G H P G G R T0.133 37 L L V P T K V T G 0.127 131 Y H F Q V P S R I 0.123 399 R K A EN G P H L 0.122 239 I A P L A A T R A 0.117 43 V T G I I T Q G A 0.11749 Q G A K D F G H V 0.112 227 G S P R G L G F I 0.112 299 T S S S T Y DS L 0.102 134 Q V P S R I F W R 0.096 382 A I E S L E E G L 0.092 194 IH Y R K N K Q L 0.081 268 P A L S A R A P V 0.079 306 S L S P Y G P R N0.075 256 R T P R A G S S A 0.069 197 R K N K Q L M R L 0.068 400 K A EN G P H L L 0.066 270 L S A R A P V P A 0.055 111 K L K Y L A F L H0.053 42 K V T G I I T Q G 0.052 393 K Q K D K E R K A 0.051 295 S S C PT S S S T 0.049 10 P L R A L H I V V 0.048 200 K Q L M R L Q K Q 0.04548 T Q G A K D F G H 0.044 204 R L Q K Q A E K N 0.037 291 W T R P S S CP T 0.036 240 A P L A A T R A T 0.036 277 P A A S P A A W L 0.036 328 GL K K P A R H C 0.035 261 G S S A H R P P A 0.032 337 Q G Q K H N V L A0.032 152 C P Q G H A S E A 0.032 325 G G G G L K K P A 0.032 274 A P VP A A S P A 0.032 266 R P P A L S A R A 0.032 236 F K T I A P L A A0.032 302 S T Y D S L S P Y 0.031 59 F V G S Y K L A Y 0.030 205 L Q K QA E K N M 0.030 64 K L A Y S N D G E 0.026 343 V L A R G K P Q R 0.025163 K V C L S G A P H 0.023 207 K Q A E K N M K K 0.022 16 I V V E S I RD H 0.021 102 N I S G S F C R N 0.019 116 A F L H K R M N T 0.019 368 AD L A G S G Y C 0.018 371 A G S G Y C G A L 0.018

[0808] TABLE VIII Pos 1 2 3 4 5 6 7 8 9 0 Score SeqID v.1-A2-10mers:151P3D4 83 K L T S D Y L K E V 559.894 40 L L V E A E Q A K V 484.777343 K L Y G V Y C F R A 322.721 6 L L V L I S I C W A 106.837 3 S L L LL V L I S I 88.783 193 Q L Y D A W R G G L 36.436 4 L L L L V L I S I C29.468 150 V V V A L D L Q G V 23.795 269 K L T Y D E A V Q A 17.388 32I Q A E N G P H L L 15.096 73 G I H K I R I K W T 12.962 48 K V F S H RG G N V 10.245 297 K I L G Y D R C D A 8.846 201 G L D W C N A G W L6.110 255 S N F N G R F Y Y L 5.392 171 N L N F H E A Q Q A 4.968 326 SP T E A A V R F V 4.710 23 T L D H D R A I H I 4.173 285 Q I A K V G Q IF A 3.757 209 W L S D G S V Q Y P 3.556 158 G V V F P Y F P R L 3.551270 L T Y D E A V Q A C 3.540 105 Y G G Y Q G R V F L 3.528 178 Q Q A CL D Q D A V 3.455 95 F V S M G Y H K K T 2.999 145 L E D D T V V V A L2.664 9 L I S I C W A D H L 2.447 116 G G S D S D A S L V 1.861 290 G QI F A A W K I L 1.510 103 K T Y G G Y Q G R V 1.406 223 R E P C G G Q NT V 1.352 130 T L E D Y G R Y K C 1.304 68 T A F G S G I H K I 1.233 144G L E D D T V V V A 1.229 14 W A D H L S D N Y T 1.047 226 C G G Q N T VP G V 1.044 166 R L G R Y N L N F H 0.943 142 I E G L E D D T V V 0.943335 V G F P D K K H K L 0.877 289 V G Q I F A A W K I 0.868 113 F L K GG S D S D A 0.800 308 W L A D G S V R Y P 0.711 280 L N D G A Q I A K V0.710 50 F S H R G G N V T L 0.641 151 V V L A D L Q G V V 0.551 122 A SL V I T D L T L 0.516 141 V I E G L E D D T V 0.510 177 A Q Q A C L D QD A 0.504 115 K G G S D S D A S L 0.488 5 L L L V L I S I C W 0.469 263Y L I H P T K L T Y 0.343 70 F G S G I H K I R I 0.313 108 Y Q G R V F LK G G 0.304 97 S M G Y H K K T Y G 0.296 76 K I R I K W T K L T 0.273188 I A S F D Q L Y D A 0.270 88 Y L K E V D V F V S 0.269 196 D A W R GG L D W C 0.266 8 V L I S I C W A D H 0.215 275 A V Q A C L N D G A0.213 143 E G L E D D T V V V 0.212 172 L N F H E A Q Q A C 0.204 180 AC L D Q D A V I A 0.202 90 K E V D V F V S M G 0.182 85 T S D Y L K E VD V 0.182 277 Q A C L N D G A Q I 0.145 245 K S R Y D V F C F T 0.135340 K K H K L Y G V Y C 0.133 206 N A G W L S D G S V 0.126 31 H I Q A EN G P H L 0.100 309 L A D G S V R Y P I 0.099 140 E V I E G L E D D T0.098 288 K V G Q I F A A W K 0.095 125 V I T D L T L E D Y 0.080 153 AL D L Q G V V F P 0.075 217 Y P I T K P R E P C 0.073 181 C L D Q D A VI A S 0.069 120 S D A S L V I T D L 0.068 163 Y F P R L G R Y N L 0.068241 W D K D K S R Y D V 0.064 298 I L G Y D R C D A G 0.062 33 Q A E N GP H L L V 0.062 7 L V L I S I C W A D 0.062 279 C L N D G A Q I A K0.061 173 N F H E A Q Q A C L 0.061 179 Q A C L D Q D A V I 0.059 155 DL Q G V V F P Y F 0.058 1 M K S L L L L V L I 0.057 42 V E A E Q A K V FS 0.056 65 R D P T A F G S G I 0.055 286 I A K V G Q I F A A 0.055 156 LQ G V V F P Y F P 0.054 278 A C L N D G A Q I A 0.049 345 Y G V Y C F RA Y N 0.047 210 L S D G S V Q Y P I 0.046 264 L I H P T K L T Y D 0.044261 F Y Y L I H P T K L 0.044 283 G A Q I A K V G Q I 0.043 56 N V T L PC K F Y R 0.042 256 N F N G R F Y Y L I 0.041 v.2-A2-10mers: 151P3D4 87V L L G R K A V V V 179.368 67 Y S N D G E H W T V 64.221 37 L L V P T KV T G I 40.792 86 K V L L G R K A V V 32.313 234 F I F K T I A P L A11.626 30 K Q D K K V D L L V 9.873 34 K V D L L V P T K V 8.520 231 G LG F I F K T I A 7.740 200 K Q L M R L Q K Q A 6.523 204 R L Q K Q A E KN M 4.968 269 A L S A R A P V P A 4.968 57 V Q F V G S Y K L A 4.752 2 LE H T T K T F P L 4.096 9 F P L R A L H I V V 3.168 164 V C L S G A P HE V 2.856 381 K A I E S L E E G L 2.086 28 K M K Q D K K V D L 1.890 7 KT F P L R A L H I 1.876 373 S G Y C G A L W K A 1.790 48 T Q G A K D F GH V 1.742 94 V V V S C E G I N I 1.552 42 K V T G I I T Q G A 1.521 276V P A A S P A A W L 1.304 377 G A L W K A I E S L 1.237 212 N M K K K ID K Y T 1.036 238 T I A P L A A T R A 0.683 115 L A F L H K R M N T0.651 183 T L E E K R K E K A 0.639 12 R A L H I V V E S I 0.604 369 D LA G S G Y C G A 0.559 361 Y V E N G R P A D L 0.550 284 W L P L R T P WT R 0.514 133 F Q V P S R I F W R 0.510 278 A A S P A A W L P L 0.504336 C Q G Q K H N V L A 0.504 51 A K D F G H V Q F V 0.489 230 R G L G FI F K T I 0.479 173 V G W K Y Q A V T A 0.458 175 W K Y Q A V T A T L0.437 59 F V G S Y K L A Y S 0.379 353 P K S E N N S W Y V 0.359 92 K AV V V S C E G I 0.249 26 G Q K M K Q D K K V 0.247 103 I S G S F C R N KL 0.237 307 L S P Y G P R N P L 0.237 29 M K Q D K K V D L L 0.233 241 PL A A T R A T R I 0.230 193 E I H Y R K N K Q L 0.220 400 K A E N G P HL L V 0.216 20 S I R D H S G Q K M 0.213 106 S F C R N K L K Y L 0.188261 G S S A H R P P A L 0.139 270 L S A R A P V P A A 0.127 378 A L W KA I E S L E 0.124 399 R K A E N G P H L L 0.122 88 L L G R K A V V V S0.119 226 G G S P R G L G F I 0.112 236 F K T I A P L A A T 0.110 38 L VP T K V T G I I 0.083 362 V E N G R P A D L A 0.080 302 S T Y D S L S PY G 0.075 155 G H A S E A Y K K V 0.072 273 R A P V P A A S P A 0.069288 R T P W T R P S S C 0.069 263 S A H R P P A L S A 0.069 171 H E V GW K Y Q A V 0.069 117 F L H K R M N T N P 0.069 114 Y L A F L H K R M N0.069 370 L A G S G Y C G A L 0.066 56 H V Q F V G S Y K L 0.064 109 K NK L K Y L A F L 0.062 201 Q L M R L Q K Q A E 0.055 207 K Q A E K N M KK K 0.050 280 S P A A W L P L R T 0.049 334 R H C Q G Q K H N V 0.048 46I I T Q G A K D F G 0.047 8 T F P L R A L H I V 0.046 239 I A P L A A TR A T 0.035 233 G F I F K T I A P L 0.034 64 K L A Y S N D G E H 0.03439 V P T K V T G I I T 0.034 151 C C P Q G H A S E A 0.032 260 A G S S AH R P P A 0.032 324 S G G G G L K K P A 0.032 274 A P V P A A S P A A0.032 223 S P G G G S P R G L 0.028 35 V D L L V P T K V T 0.027 343 V LA R G K P Q R K 0.025 327 G G L K K P A R H C 0.024 16 I V V E S I R D HS 0.022 283 A W L P L R T P W T 0.021 36 D L L V P T K V T G 0.021 172 EV G W K Y Q A V T 0.020 194 I H Y R K N K Q L M 0.019 134 Q V P S R I FW R Q 0.019 165 C L S G A P H E V G 0.015 216 K I D K Y T E S P G 0.01499 E G I N I S G S F C 0.013 100 G I N I S G S F C R 0.012 77 Y Q D E KQ R K D K 0.011

[0809] TABLE IX Pos 1 2 3 4 5 6 7 8 9 Score SeqID v.1-A3-9mers: 151P3D4343 K L Y G V Y C F R 135.000 40 L L V E A E Q A K 45.000 155 D L Q G VV F P Y 24.300 166 R L G R Y N L N F 12.000 158 G V V F P Y F P R 8.100130 T L E D Y G R Y K 6.000 103 K T Y G G Y Q G R 4.500 159 V V F P Y FP R L 4.050 4 L L L L V L I S I 4.050 308 W L A D G S V R Y 4.000 209 WL S D G S V Q Y 4.000 128 D L T L E D Y G R 3.600 68 T A F G S G I H K3.000 213 G S V Q Y P I T K 2.700 153 A L D L Q G V V F 2.000 95 F V S MG Y H K K 2.000 97 S M G Y H K K T Y 2.000 123 S L V I T D L T L 1.80057 V T L P C K F Y R 1.350 187 V I A S F D Q L Y 1.200 264 L I H P T K LT Y 1.200 249 D V F C F T S N F 0.900 6 L L V L I S I C W 0.900 107 G YQ G R V F L K 0.810 215 V Q Y P I T K P R 0.675 144 G L E D D T V V V0.600 201 G L D W C N A G W 0.600 161 F P Y F P R L G R 0.600 312 G S VR Y P I S R 0.540 88 Y L K E V D V F V 0.450 5 L L L V L I S I C 0.450 3S L L L L V L I S 0.360 56 N V T L P C K F Y 0.300 39 H L L V E A E Q A0.300 285 Q I A K V G Q I F 0.300 332 V R F V G F P D K 0.300 126 I T DL T L E D Y 0.300 245 K S R Y D V F C F 0.270 156 L Q G V V F P Y F0.270 186 A V I A S F D Q L 0.270 288 K V G Q I F A A W 0.270 290 G Q IF A A W K I 0.243 181 C L D Q D A V I A 0.200 23 T L D H D T A I H 0.200279 C L N D G A Q I A 0.200 298 I L G Y D R C D A 0.200 235 V R N Y G FW D K 0.180 76 K I R I K W T K L 0.180 73 G I H K I R I K W 0.180 58 T LP C K F Y R D 0.180 228 G Q N T V P G V R 0.162 45 E Q A K V F S H R0.162 261 F Y Y L I H P T K 0.150 291 Q I F A A W K I L 0.150 230 N T VP G V R N Y 0.135 8 V L I S I C W A D 0.135 75 H K I R I K W T K 0.135333 R F V G F P D K K 0.135 129 L T L E D Y G R Y 0.135 280 L N D G A QI A K 0.120 293 F A A W K I L G Y 0.120 255 S N F N G R F Y Y 0.120 83 KL T S D Y L K E 0.120 263 Y L I H P T K L T 0.113 54 G G N V T L P C K0.090 94 V F V S M G Y H K 0.090 82 T K L T S D Y L K 0.090 253 F T S NF N G R F 0.090 346 G V Y C F R A Y N 0.090 335 V G F P D K K H K 0.075289 V G Q I F A A W K 0.060 269 K L T Y D E A V Q 0.060 232 V P G V R NY G F 0.060 234 G V R N Y G F W D 0.054 270 L T Y D E A V Q A 0.050 7 LV L I S I C W A 0.045 183 D Q D A V I A S F 0.041 148 D T V V V A L D L0.041 14 W A D H L S D N Y 0.040 62 K F Y R D P T A F 0.030 239 G F W DK D K S R 0.030 237 N Y G F W D K D K 0.030 151 V V A L D L Q G V 0.030326 S P T E A A V R F 0.030 81 W T K L T S D Y L 0.030 113 F L K G G S DS D 0.030 32 I Q A E N G P H L 0.027 342 H K L Y G V Y C F 0.027 284 A QI A K V G Q I 0.024 84 L T S D Y L K E V 0.022 189 A S F D Q L Y D A0.022 2 K S L L L L V L I 0.020 325 C S P T E A A V R 0.020 9 L I S I CW A D H 0.020 337 F P D K K H K L Y 0.020 171 N L N F H E A Q Q 0.020 41L V E A E Q A K V 0.020 17 H L S D N Y T L D 0.020 55 G N V T L P C K F0.018 92 V D V F V S M G Y 0.018 v.2-A3-9mers: 151P3D4 389 G L G G K Q KD K 45.000 34 K V D L L V P T K 18.000 183 T L E E K R K E K 15.000 385S L E E G L G G K 13.500 212 N M K K K I D K Y 6.000 207 K Q A E K N M KK 5.400 378 A L W K A I E S L 4.500 231 G L G F I F K T I 4.050 121 R MN T N P S R R 4.000 343 V L A R G K P Q R 4.000 179 A V T A T L E E K3.000 56 H V Q F V G S Y K 3.000 13 A L H I V V E S I 2.700 59 F V G S YK L A Y 2.400 338 G Q K H N V L A R 2.160 26 G Q K M K Q D K K 1.800 111K L K Y L A F L H 1.800 134 Q V P S R I F W R 1.800 302 S T Y D S L S PY 1.500 75 T V Y Q D E K Q R 1.000 1 M L E H T T K T F 1.000 105 G S F CR N K L K 0.750 20 S I R D H S G Q K 0.600 112 L K Y L A F L H K 0.600 4H T T K T F P L R 0.600 238 T I A P L A A T R 0.600 168 G A P H E V G WK 0.540 87 V L L G R K A V V 0.450 234 F I F K T I A P L 0.450 241 P L AA T R A T R 0.400 211 K N M K K K I D K 0.360 344 L A R G K P Q R K0.300 165 C L S G A P H E V 0.300 57 V Q F V G S Y K L 0.270 169 A P H EV G W K Y 0.270 7 K T F P L R A L H 0.225 88 L L G R K A V V V 0.200 373S G Y C G A L W K 0.200 180 V T A T L E E K R 0.200 155 G H A S E A Y KK 0.180 280 S P A A W L P L R 0.180 285 L P L R T P W T R 0.180 38 L V PT K V T G I 0.180 30 K Q D K K V D L L 0.162 208 Q A E K N M K K K 0.150201 Q L M R L Q K Q A 0.150 358 N S W Y V E N G R 0.150 192 A E I H Y RK N K 0.135 95 V V S C E G I N I 0.120 284 W L P L R T P W T 0.100 46 II T Q G A K D F 0.100 138 R I F W R Q E K A 0.100 114 Y L A F L H K R M0.100 181 T A T L E E K R K 0.100 137 S R I F W R Q E K 0.090 306 S L SP Y G P R N 0.090 228 S P R G L G F I F 0.090 93 A V V V S C E G I 0.090328 G L K K P A R H C 0.090 322 S P S G G G G L K 0.090 113 K Y L A F LH K R 0.081 308 S P Y G P R N P L 0.068 392 G K Q K D K E R K 0.060 73 HW T V Y Q D E K 0.060 382 A I E S L E E G L 0.060 64 K L A Y S N D G E0.060 5 T T K T F P L R A 0.060 163 K V C L S G A P H 0.060 125 N P S RR P Y H F 0.060 100 G I N I S G S F C 0.060 81 K Q R K D K V L L 0.054189 K E K A E I H Y R 0.054 237 K T I A P L A A T 0.051 55 G H V Q F V GS Y 0.049 37 L L V P T K V T G 0.045 86 K V L L G R K A V 0.045 190 E KA E I H Y R K 0.041 199 N K Q L M R L Q K 0.040 296 S C P T S S S T Y0.040 10 P L R A L H I V V 0.040 101 I N I S G S F C R 0.036 36 D L L VP T K V T 0.034 323 P S G G G G L K K 0.030 103 I S G S F C R N K 0.030203 M R L Q K Q A E K 0.030 117 F L H K R M N T N 0.030 28 K M K Q D K KV D 0.030 123 N T N P S R R P Y 0.030 369 D L A G S G Y C G 0.027 133 FQ V P S R I F W 0.027 84 K D K V L L G R K 0.027 42 K V T G I I T Q G0.020 204 R L Q K Q A E K N 0.020 25 S G Q K M K Q D K 0.020 206 Q K Q AE K N M K 0.020 244 A T R A T R I G H 0.020 202 L M R L Q K Q A E 0.020154 Q G H A S E A Y K 0.020 269 A L S A R A P V P 0.020 76 V Y Q D E K QR K 0.020

[0810] TABLE X Pos 1 2 3 4 5 6 7 8 9 0 Score SeqID v.1-A3-10mers:151P3D4 234 G V R N Y G F W D K 54.000 343 K L Y G V Y C F R A 40.500279 C L N D G A Q I A K 40.000 39 H L L V E A E Q A K 30.000 288 K V G QI F A A W K 18.000 263 Y L I H P T K L T Y 12.000 93 D V F V S M G Y H K9.000 331 A V R F V G F P D K 6.000 155 D L Q G V V F P Y F 4.050 3 S LL L L V L I S I 4.050 81 W T K L T S D Y L K 3.000 106 G G Y Q G R V F LK 2.700 193 Q L Y D A W R G G L 2.700 158 G V V F P Y F P R L 2.430 186A V I A S F D Q L Y 1.800 144 G L E D D T V V V A 1.800 83 K L T S D Y LK E V 1.350 23 T L D H D R A I H I 1.200 17 H L S D N Y T L D H 1.200 56N V T L P C K F Y R 1.200 334 F V G F P D K K H K 1.000 5 L L L V L I SI C W 0.900 231 T V P G V R N Y G F 0.900 129 L T L E D Y G R Y K 0.675125 V I T D L T L E D Y 0.600 130 T L E D Y G R Y K C 0.600 294 A A W KI L G Y D R 0.600 269 K L T Y D E A V Q A 0.600 251 F C F T S N F N G R0.600 201 G L D W C N A G W L 0.540 88 Y L K E V D V F V S 0.540 4 L L LL V L I S I C 0.450 236 R N Y G F W D K D K 0.450 40 L L V E A E Q A K V0.450 6 L L V L I S I C W A 0.450 91 E V D V F V S M G Y 0.360 128 D L TL E D Y G R Y 0.360 113 F L K G G S D S D A 0.300 214 S V Q Y P I T K PR 0.300 8 V L I S I C W A D H 0.300 332 V R F V G F P D K K 0.300 166 RL G R Y N L N F H 0.300 181 C L D Q D A V I A S 0.240 103 K T Y G G Y QG R V 0.203 171 N L N F H E A Q Q A 0.200 67 P T A F G S G I H K 0.200 9L I S I C W A D H L 0.180 260 R F Y Y L I H P T K 0.150 270 L T Y D E AV Q A C 0.150 284 A Q I A K V G Q I F 0.135 297 K I L G Y D R C D A0.135 41 L V E A E Q A K V F 0.100 74 I H K I R I K W T K 0.090 161 F PY F P R L G R Y 0.090 48 K V F S H R G G N V 0.090 154 L D L Q G V V F PY 0.081 68 T A F G S G I H K I 0.068 239 G F W D K D K S R Y 0.060 324 RC S P T E A A V R 0.060 313 S V R Y P I S R P R 0.060 153 A L D L Q G VV F P 0.060 291 Q I F A A W K I L G 0.060 254 T S N F N G R F Y Y 0.060209 W L S D G S V Q Y P 0.060 31 H I Q A E N G P H L 0.060 341 K H K L YG V Y C F 0.054 255 S N F N G R F Y Y L 0.054 44 A E Q A K V F S H R0.054 123 S L V I T D L T L E 0.045 71 G S G I H K I R I K 0.045 150 V VV A L D L Q G V 0.045 76 K I R I K W T K L T 0.045 309 L A D G S V R Y PI 0.041 290 G Q I F A A W K I L 0.041 285 Q I A K V G Q I F A 0.040 212D G S V Q Y P I T K 0.036 53 R G G N V T L P C K 0.030 94 V F V S M G YH K K 0.030 314 V R Y P I S R P R R 0.030 141 V I E G L E D D T V 0.030152 V A L D L Q G V V F 0.030 86 S D Y L K E V D V F 0.030 55 G N V T LP C K F Y 0.027 157 Q G V V F P Y F P R 0.027 32 I Q A E N G P H L L0.027 73 G I H K I R I K W T 0.022 96 V S M G Y H K K T Y 0.022 57 V T LP C K F Y R D 0.020 210 L S D G S V Q Y P I 0.020 298 I L G Y D R C D AG 0.020 111 R V F L K G G S D S 0.020 97 S M G Y H K K T Y G 0.020 275 AV Q A C L N D G A 0.020 253 F T S N F N G R F Y 0.020 306 A G W L A D GS V R 0.020 79 I K W T K L T S D Y 0.020 208 G W L S D G S V Q Y 0.018307 G W L A D G S V R Y 0.018 127 T D L T L E D Y G R 0.018 328 T E A AV R F V G F 0.018 v.2-A3-10mers: 151P3D4 111 K L K Y L A F L H K 360.000202 L M R L Q K Q A E K 20.000 343 V L A R G K P Q R K 20.000 284 W L PL R T P W T R 12.000 75 T V Y Q D E K Q R K 10.000 13 A L H I V V E S IR 6.000 37 L L V P T K V T G I 4.050 100 G I N I S G S F C R 3.600 207 KQ A E K N M K K K 2.025 228 S P R G L G F I F K 1.800 28 K M K Q D K K VD L 1.800 231 G L G F I F K T I A 1.800 7 K T F P L R A L H I 1.350 133F Q V P S R I F W R 1.215 182 A T L E E K R K E K 1.125 237 K T I A P LA A T R 0.900 191 K A E I H Y R K N K 0.900 102 N I S G S F C R N K0.900 189 K E K A E I H Y R K 0.810 372 G S G Y C G A L W K 0.600 322 SP S G G G G L K K 0.600 342 N V L A R G K P Q R 0.600 105 G S F C R N KL K Y 0.600 129 R P Y H F Q V P S R 0.600 205 L Q K Q A E K N M K 0.600168 G A P H E V G W K Y 0.540 180 V T A T L E E K R K 0.500 178 Q A V TA T L E E K 0.450 87 V L L G R K A V V V 0.450 45 G I I T Q G A K D F0.450 77 Y Q D E K Q R K D K 0.450 179 A V T A T L E E K R 0.400 183 T LE E K R K E K A 0.300 43 V T G I I T Q G A K 0.300 33 K K V D L L V P TK 0.270 198 K N K Q L M R L Q K 0.240 269 A L S A R A P V P A 0.200 64 KL A Y S N D G E H 0.180 94 V V V S C E G I N I 0.180 56 H V Q F V G S YK L 0.180 331 K P A R H C Q G Q K 0.180 74 W T V Y Q D E K Q R 0.150 234F I F K T I A P L A 0.150 378 A L W K A I E S L E 0.150 55 G H V Q F V GS Y K 0.135 42 K V T G I I T Q G A 0.135 352 K P K S E N N S W Y 0.120311 G P R N P L P N P R 0.120 88 L L G R K A V V V S 0.120 24 H S G Q KM K Q D K 0.100 204 R L Q K Q A E K N M 0.100 279 A S P A A W L P L R0.090 34 K V D L L V P T K V 0.090 369 D L A G S G Y C G A 0.090 112 L KY L A F L H K R 0.090 86 K V L L G R K A V V 0.090 389 G L G G K Q K D KE 0.090 227 G S P R G L G F I F 0.090 72 E H W T V Y Q D E K 0.090 212 NM K K K I D K Y T 0.075 391 G G K Q K D K E R K 0.060 154 Q G H A S E AY K K 0.060 153 P Q G H A S E A Y K 0.060 50 G A K D F G H V Q F 0.060152 C P Q G H A S E A Y 0.060 240 A P L A A T R A T R 0.060 361 Y V E NG R P A D L 0.060 241 P L A A T R A T R I 0.060 247 A T R I G H P G G R0.060 328 G L K K P A R H C Q 0.060 4 H T T K T F P L R A 0.060 211 K NM K K K I D K Y 0.054 58 Q F V G S Y K L A Y 0.054 30 K Q D K K V D L LV 0.054 47 I T Q G A K D F G H 0.045 165 C L S G A P H E V G 0.045 386 LE E G L G G K Q K 0.045 381 K A I E S L E E G L 0.041 377 G A L W K A IE S L 0.041 12 R A L H I V V E S I 0.041 257 T P R A G S S A H R 0.040366 R P A D L A G S G Y 0.040 206 Q K Q A E K N M K K 0.040 187 K R K EK A E I H Y 0.036 384 E S L E E G L G G K 0.030 136 P S R I F W R Q E K0.030 295 S S C P T S S S T Y 0.030 301 S S T Y D S L S P Y 0.030 201 QL M R L Q K Q A E 0.030 238 T I A P L A A T R A 0.030 321 H S P S G G GG L K 0.030 38 L V P T K V T G I I 0.027 167 S G A P H E V G W K 0.02792 K A V V V S C E G I 0.027 134 Q V P S R I F W R Q 0.027 337 Q G Q K HN V L A R 0.024 1 M L E H T T K T F P 0.020 117 F L H K R M N T N P0.020 20 S I R D H S G Q K M 0.020 25 S G Q K M K Q D K K 0.020

[0811] TABLE XI Pos 1 2 3 4 5 6 7 8 9 Score SeqID v.1-A11-9mers: 151P3D4158 G V V F P Y F P R 5.400 107 G Y Q G R V F L K 3.600 95 F V S M G Y HK K 2.000 103 K T Y G G Y Q G R 1.200 57 V T L P C K F Y R 0.900 333 R FV G F P D K K 0.900 68 T A F G S G I H K 0.800 261 F Y Y L I H P T K0.800 94 V F V S M G Y H K 0.600 40 L L V E A E Q A K 0.600 343 K L Y GV Y C F R 0.480 228 G Q N T V P G V R 0.360 315 R Y P I S R P R R 0.240237 N Y G F W D K D K 0.200 213 G S V Q Y P I T K 0.180 161 F P Y F P RL G R 0.160 239 G F W D K D K S R 0.120 215 V Q Y P I T K P R 0.120 280L N D G A Q I A K 0.080 75 H K I R I K W T K 0.060 82 T K L T S D Y L K0.060 54 G G N V T L P C K 0.060 288 K V G Q I F A A W 0.060 290 G Q I FA A W K I 0.054 128 D L T L E D Y G R 0.048 130 T L E D Y G R Y K 0.040252 C F T S N F N G R 0.040 332 V R F V G F P D K 0.040 235 V R N Y G FW D K 0.040 159 V V F P Y F P R L 0.040 312 G S V R Y P I S R 0.036 45 EQ A K V F S H R 0.036 186 A V I A S F D Q L 0.030 7 L V L I S I C W A0.030 73 G I H K I R I K W 0.024 166 R L G R Y N L N F 0.024 270 L T Y DE A V Q A 0.020 335 V G F P D K K H K 0.020 151 V V A L D L Q G V 0.020289 V G Q I F A A W K 0.020 41 L V E A E Q A K V 0.020 307 G W L A D G SV R 0.018 234 G V R N Y G F W D 0.018 129 L T L E D Y G R Y 0.015 201 GL D W C N A G W 0.012 346 G V Y C F R A Y N 0.012 169 R Y N L N F H E A0.012 4 L L L L V L I S I 0.012 249 D V F C F T S N F 0.012 6 L L V L IS I C W 0.012 144 G L E D D T V V V 0.012 300 G Y D R C D A G W 0.012 76K I R I K W T K L 0.012 48 K V F S H R G G N 0.012 62 K F Y R D P T A F0.012 111 R V F L K G G S D 0.012 123 S L V I T D L T L 0.012 344 L Y GV Y C F R A 0.012 93 D V F V S M G Y H 0.012 253 F T S N F N G R F 0.01056 N V T L P C K F Y 0.010 334 F V G F P D K K H 0.010 126 I T D L T L ED Y 0.010 81 W T K L T S D Y L 0.010 148 D T V V V A L D L 0.009 284 A QI A K V G Q I 0.009 264 L I H P T K L T Y 0.008 295 A W K I L G Y D R0.008 316 Y P I S R P R R R 0.006 178 Q Q A C L D Q D A 0.006 324 R C SP T E A A V 0.006 150 V V V A L D L Q G 0.006 276 V Q A C L N D G A0.006 32 I Q A E N G P H L 0.006 331 A V R F V G F P D 0.006 262 Y Y L IH P T K L 0.006 39 H L L V E A E Q A 0.006 156 L Q G V V F P Y F 0.006336 G F P D K K H K L 0.006 84 L T S D Y L K E V 0.005 20 D N Y T L D HD R 0.005 9 L I S I C W A D H 0.004 104 T Y G G Y Q G R V 0.004 325 C SP T E A A V R 0.004 293 F A A W K I L G Y 0.004 291 Q I F A A W K I L0.004 256 N F N G R F Y Y L 0.004 164 F P R L G R Y N L 0.004 232 V P GV R N Y G F 0.004 298 I L G Y D R C D A 0.004 209 W L S D G S V Q Y0.004 153 A L D L Q G V V F 0.004 279 C L N D G A Q I A 0.004 286 I A KV G Q I F A 0.004 194 L Y D A W R G G L 0.004 191 F D Q L Y D A W R0.004 181 C L D Q D A V I A 0.004 31 H I Q A E N G P H 0.004 308 W L A DG S V R Y 0.004 88 Y L K E V D V F V 0.004 v.2-A11-9mers: 151P3D4 34 K VD L L V P T K 6.000 207 K Q A E K N M K K 3.600 56 H V Q F V G S Y K2.000 179 A V T A T L E E K 2.000 26 G Q K M K Q D K K 1.800 134 Q V P SR I F W R 1.200 338 G Q K H N V L A R 0.720 389 G L G G K Q K D K 0.600168 G A P H E V G W K 0.600 211 K N M K K K I D K 0.480 75 T V Y Q D E KQ R 0.400 385 S L E E G L G G K 0.400 76 V Y Q D E K Q R K 0.400 20 S IR D H S G Q K 0.400 113 K Y L A F L H K R 0.360 121 R M N T N P S R R0.240 322 S P S G G G G L K 0.200 344 L A R G K P Q R K 0.200 4 H T T KT F P L R 0.200 183 T L E E K R K E K 0.200 180 V T A T L E E K R 0.200155 G H A S E A Y K K 0.120 285 L P L R T P W T R 0.120 208 Q A E K N MK K K 0.100 181 T A T L E E K R K 0.100 238 T I A P L A A T R 0.080 343V L A R G K P Q R 0.080 373 S G Y C G A L W K 0.080 112 L K Y L A F L HK 0.080 84 K D K V L L G R K 0.060 105 G S F C R N K L K 0.060 392 G K QK D K E R K 0.060 7 K T F P L R A L H 0.060 163 K V C L S G A P H 0.06086 K V L L G R K A V 0.045 192 A E I H Y R K N K 0.045 280 S P A A W L PL R 0.040 95 V V S C E G I N I 0.040 199 N K Q L M R L Q K 0.040 59 F VG S Y K L A Y 0.040 101 I N I S G S F C R 0.036 111 K L K Y L A F L H0.036 189 K E K A E I H Y R 0.036 22 R D H S G Q K M K 0.030 346 R G K PQ R K P K 0.030 203 M R L Q K Q A E K 0.030 44 T G I I T Q G A K 0.030137 S R I F W R Q E K 0.030 256 R T P R A G S S A 0.030 93 A V V V S C EG I 0.030 83 R K D K V L L G R 0.024 120 K R M N T N P S R 0.024 138 R IF W R Q E K A 0.024 57 V Q F V G S Y K L 0.024 374 G Y C G A L W K A0.024 5 T T K T F P L R A 0.020 25 S G Q K M K Q D K 0.020 332 P A R H CQ G Q K 0.020 38 L V P T K V T G I 0.020 206 Q K Q A E K N W K 0.020 244A T R A T R I G H 0.020 302 S T Y D S L S P Y 0.020 73 H W T V Y Q D E K0.020 154 Q G H A S E A Y K 0.020 81 K Q R K D K V L L 0.018 133 F Q V PS R I F W 0.018 48 T Q G A K D F G H 0.018 30 K Q D K K V D L L 0.018326 G G G L K K P A R 0.012 251 G H P G G R T P R 0.012 176 K Y Q A V TA T L 0.012 190 E K A E I H Y R K 0.012 78 Q D E K Q R K D K 0.010 43 VT G I I T Q G A 0.010 387 E E G L G G K Q K 0.009 241 P L A A T R A T R0.008 130 P Y H F Q V P S R 0.008 378 A L W K A I E S L 0.008 358 N S WY V E N G R 0.008 196 Y R K N K Q L M R 0.008 234 F I F K T I A P L0.008 14 L H I V V E S I R 0.006 391 G G K Q K D K E R 0.006 340 K H N VL A R G K 0.006 248 T R I G H P G G R 0.006 87 V L L G R K A V V 0.006172 E V G W K Y Q A V 0.006 400 K A E N G P H L L 0.006 352 K P K S E NN S W 0.006 42 K V T G I I T Q G 0.006 228 S P R G L G F I F 0.006 231 GL G F I F K T I 0.006 336 C Q G Q K H N V L 0.006 266 R P P A L S A R A0.006 237 K T I A P L A A T 0.005 323 P S G G G G L K K 0.004 229 P R GL G F I F K 0.004 169 A P H E V G W K Y 0.004 308 S P Y G P R N P L0.004 106 S F C R N K L K Y 0.004

[0812] TABLE XII Pos 1 2 3 4 5 6 7 8 9 0 Score SeqID v.1-A11-10mers:151P3D4 234 G V R N Y G F W D K 12.000 288 K V G Q I F A A W K 6.000 93D V F V S M G Y H K 2.400 81 W T K L T S D Y L K 2.000 331 A V R F V G FP D K 2.000 260 R F Y Y L I H P T K 1.200 56 N V T L P C K F Y R 1.200334 F V G F P D K K H K 1.000 279 C L N D G A Q I A K 0.800 39 H L L V EA E Q A K 0.600 106 G G Y Q G R V F L K 0.360 94 V F V S M G Y H K K0.300 67 P T A F G S G I H K 0.200 214 S V Q Y P I T K P R 0.200 294 A AW K I L G Y D R 0.160 129 L T L E D Y G R Y K 0.150 236 R N Y G F W D KD K 0.120 324 R C S P T E A A V R 0.120 48 K V F S H R G G N V 0.120 158G V V F P Y F P R L 0.090 160 V F P Y F P R L G R 0.080 251 F C F T S NF N G R 0.080 343 K L Y G V Y C F R A 0.072 53 R G G N V T L P C K 0.060103 K T Y G G Y Q G R V 0.060 74 I H K I R I K W T K 0.040 190 S F D Q LY D A W R 0.040 231 T V P G V R N Y G F 0.040 332 V R F V G F P D K K0.040 313 S V R Y P I S R P R 0.040 186 A V I A S F D Q L Y 0.030 150 VV V A L D L Q G V 0.030 315 R Y P I S R P R R R 0.024 275 A V Q A C L ND G A 0.020 69 A F G S G I H K I R 0.020 151 V V A L D L Q G V V 0.020157 Q G V V F P Y F P R 0.018 297 K I L G Y D R C D A 0.018 22 Y T L D HD R A I H 0.015 290 G Q I F A A W K I L 0.013 102 K K T Y G G Y Q G R0.012 127 T D L T L E D Y G R 0.012 227 G G Q N T V P G V R 0.012 111 RV F L K G G S D S 0.012 136 R Y K C E V I E G L 0.012 300 G Y D R C D AG W L 0.012 44 A E Q A K V F S H R 0.012 91 E V D V F V S M G Y 0.012239 G F W D K D K S R Y 0.012 263 Y L I H P T K L T Y 0.012 144 G L E DD T V V V A 0.012 212 D G S V Q Y P I T K 0.012 166 R L G R Y N L N F H0.012 5 L L L V L I S I C W 0.012 3 S L L L L V L I S I 0.012 201 G L DW C N A G W L 0.012 99 G Y H K K T Y G G Y 0.012 269 K L T Y D E A V Q A0.012 41 L V E A E Q A K V F 0.010 284 A Q I A K V G Q I F 0.009 306 A GW L A D G S V R 0.008 314 V R Y P I S R P R R 0.008 23 T L D H D R A I HI 0.008 17 H L S D N Y T L D H 0.008 261 F Y Y L I H P T K L 0.008 285 QI A K V G Q I F A 0.008 193 Q L Y D A W R G G L 0.008 71 G S G I H K I RI K 0.006 342 H K L Y G V Y C F R 0.006 7 L V L I S I C W A D 0.006 124L V I T D L T L E D 0.006 286 I A K V G Q I F A A 0.006 6 L L V L I S IC W A 0.006 149 T V V V A L D L Q G 0.006 178 Q Q A C L D Q D A V 0.00632 I Q A E N G P H L L 0.006 8 V L I S I C W A D H 0.006 40 L L V E A EQ A K V 0.006 283 G A Q I A K V G Q I 0.006 177 A Q Q A C L D Q D A0.006 83 K L T S D Y L K E V 0.006 333 R F V G F P D K K H 0.005 19 S DN Y T L D H D R 0.004 9 L I S I C W A D H L 0.004 188 I A S F D Q L Y DA 0.004 163 Y F P R L G R Y N L 0.004 256 N F N G R F Y Y L I 0.004 171N L N F H E A Q Q A 0.004 271 T Y D E A V Q A C L 0.004 125 V I T D L TL E D Y 0.004 33 Q A E N G P H L L V 0.004 31 H I Q A E N G P H L 0.004292 I F A A W K I L G Y 0.004 113 F L K G G S D S D A 0.004 68 T A F G SG I H K I 0.004 309 L A D G S V R Y P I 0.004 161 F P Y F P R L G R Y0.004 238 Y G F W D K D K S R 0.004 141 V I E G L E D D T V 0.004 336 GF P D K K H K L Y 0.003 v.2-A11-10mers: 151P3D4 75 T V Y Q D E K Q R K4.000 111 K L K Y L A F L H K 2.400 43 V T G I I T Q G A K 1.000 207 K QA E K N M K K K 0.900 237 K T I A P L A A T R 0.900 182 A T L E E K R KE K 0.750 100 G I N I S G S F C R 0.720 205 L Q K Q A E K N M K 0.600342 N V L A R G K P Q R 0.600 331 K P A R H C Q G Q K 0.600 133 F Q V PS R I F W R 0.540 180 V T A T L E E K R K 0.500 343 V L A R G K P Q R K0.400 228 S P R G L G F I F K 0.400 322 S P S G G G G L K K 0.400 202 LM R L Q K Q A E K 0.400 179 A V T A T L E E K R 0.400 189 K E K A E I HY R K 0.360 178 Q A V T A T L E E K 0.300 191 K A E I H Y R K N K 0.30077 Y Q D E K Q R K D K 0.300 198 K N K Q L M R L Q K 0.240 129 R P Y H FQ V P S R 0.240 247 A T R I G H P G G R 0.200 195 H Y R K N K Q L M R0.160 284 W L P L R T P W T R 0.160 74 W T V Y Q D E K Q R 0.150 372 G SG Y C G A L W K 0.120 311 G P R N P L P N P R 0.120 7 K T F P L R A L HI 0.120 55 G H V Q F V G S Y K 0.090 33 K K V D L L V P T K 0.090 86 K VL L G R K A V V 0.090 13 A L H I V V E S I R 0.080 391 G G K Q K D K E RK 0.060 153 P Q G H A S E A Y K 0.060 83 R K D K V L L G R K 0.060 94 VV V S C E G I N I 0.060 34 K V D L L V P T K V 0.060 42 K V T G I I T QG A 0.060 240 A P L A A T R A T R 0.060 206 Q K Q A E K N M K K 0.040154 Q G H A S E A Y K K 0.040 102 N I S G S F C R N K 0.040 257 T P R AG S S A H R 0.040 56 H V Q F V G S Y K L 0.040 30 K Q D K K V D L L V0.036 386 L E E G L G G K Q K 0.030 256 R T P R A G S S A H 0.030 47 I TQ G A K D F G H 0.030 120 K R M N T N P S R R 0.024 25 S G Q K M K Q D KK 0.020 38 L V P T K V T G I I 0.020 167 S G A P H E V G W K 0.020 321 HS P S G G G G L K 0.020 4 H T T K T F P L R A 0.020 24 H S G Q K M K Q DK 0.020 361 Y V E N G R P A D L 0.020 200 K Q L M R L Q K Q A 0.013 188R K E K A E I H Y R 0.012 325 G G G G L K K P A R 0.012 64 K L A Y S N DG E H 0.012 210 E K N M K K K I D K 0.012 400 K A E N G P H L L V 0.01272 E H W T V Y Q D E K 0.012 231 G L G F I F K T I A 0.012 28 K M K Q DK K V D L 0.012 221 T E S P G G G S P R 0.012 168 G A P H E V G W K Y0.012 104 S G S F C R N K L K 0.010 123 N T N P S R R P Y H 0.010 21 I RD H S G Q K M K 0.010 345 A R G K P Q R K P K 0.010 45 G I I T Q G A K DF 0.009 19 E S I R D H S G Q K 0.009 26 G Q K M K Q D K K V 0.009 113 KY L A F L H K R M 0.009 233 G F I F K T I A P L 0.009 92 K A V V V S C EG I 0.009 12 R A L H I V V E S I 0.009 377 G A L W K A I E S L 0.009 384E S L E E G L G G K 0.009 381 K A I E S L E E G L 0.009 82 Q R K D K V LL G R 0.008 234 F I F K T I A P L A 0.008 337 Q G Q K H N V L A R 0.008357 N N S W Y V E N G R 0.008 112 L K Y L A F L H K R 0.008 374 G Y C GA L W K A I 0.006 163 K V C L S G A P H E 0.006 9 F P L R A L H I V V0.006 352 K P K S E N N S W Y 0.006 50 G A K D F G H V Q F 0.006 336 C QG Q K H N V L A 0.006 37 L L V P T K V T G I 0.006 204 R L Q K Q A E K NM 0.006 58 Q F V G S Y K L A Y 0.006 57 V Q F V G S Y K L A 0.006 366 RP A D L A G S G Y 0.006 273 R A P V P A A S P A 0.006

[0813] TABLE XIII Pos 1 2 3 4 5 6 7 8 9 Score Seq ID v.1-A24-9mers:151P3D4 262 Y Y L I H P T K L 330.000 194 L Y D A W R G G L 200.000 87 DY L K E V D V F 150.000 336 G F P D K K H K L 39.600 256 N F N G R F Y YL 36.000 62 K F Y R D P T A F 20.000 169 R Y N L N F H E A 19.800 247 RY D V F C F T S 10.000 76 K I R I K W T K L 8.800 148 D T V V V A L D L8.400 271 T Y D E A V Q A C 7.200 186 A V I A S F D Q L 7.200 10 I S I CW A D H L 6.000 33 Q A E N G P H L L 6.000 123 S L V I T D L T L 6.000159 V V F P Y F P R L 5.760 121 D A S L V I T D L 5.600 133 D Y G R Y KC E V 5.500 69 A F G S G I H K I 5.500 344 L Y G V Y C F R A 5.000 300 GY D R C D A G W 5.000 21 N Y T L D H D R A 5.000 104 T Y G G Y Q G R V5.000 32 I Q A E N G P H L 4.800 116 G G S D S D A S L 4.800 245 K S R YD V F C F 4.000 164 F P R L G R Y N L 4.000 166 R L G R Y N L N F 4.00081 W T K L T S D Y L 4.000 291 Q I F A A W K I L 4.000 106 G G Y Q G R VF L 4.000 55 G N V T L P C K F 3.960 2 K S L L L L V L I 3.600 156 L Q GV V F P Y F 3.360 285 Q I A K V G Q I F 3.360 183 D Q D A V I A S F2.800 329 E A A V R F V G F 2.400 326 S P T E A A V R F 2.400 4 L L L LV L I S I 2.100 249 D V F C F T S N F 2.000 232 V P G V R N Y G F 2.000105 Y G G Y Q G R V F 2.000 253 F T S N F N G R F 2.000 153 A L D L Q GV V F 2.000 22 Y T L D H D R A I 1.800 180 A C L D Q D A V I 1.800 290 GQ I F A A W K I 1.650 284 A Q I A K V G Q I 1.500 278 A C L N D G A Q I1.500 315 R Y P I S R P R R 1.500 260 R F Y Y L I H P T 1.200 36 R Y K CE V I E G 1.100 134 Y G R Y K C E V I 1.000 71 G S G I H K I R I 1.000257 F N G R F Y Y L I 1.000 66 D P T A F G S G I 1.000 163 Y F P R L G RY N 0.900 272 Y D E A V Q A C L 0.840 112 V F L K G G S D S 0.750 216 QY P I T K P R E 0.750 107 G Y Q G R V F L K 0.750 173 N F H E A Q Q A C0.720 261 F Y Y L I H P T K 0.700 537 Y K C E V I E G L 0.672 190 S F DQ L Y D A W 0.600 250 V F C F T S N F N 0.600 162 P Y F P R L G R Y0.600 63 F Y R D P T A F G 0.600 16 D H L S D N Y T L 0.600 174 F H E AQ Q A C L 0.600 146 E D D T V V V A L 0.560 99 G Y H K K T Y G G 0.500237 N Y G F W D K D K 0.500 49 V F S H R G G N V 0.500 1 M K S L L L L VL 0.480 28 R A I H I Q A E N 0.462 51 S H R G G N V T L 0.400 243 K D KS R Y D V F 0.400 202 L D W C N A G W L 0.400 301 Y D R C D A G W L0.400 288 K V G Q I F A A W 0.336 90 K E V D V F V S M 0.302 342 H K L YG V Y C F 0.300 53 R G G N V T L P C 0.280 324 R C S P T E A A V 0.24042 V E A E Q A K V F 0.240 80 K W T K L T S D Y 0.240 152 V A L D L Q GV V 0.216 279 C L N D G A Q I A 0.216 155 D L Q G V V F P Y 0.210 122 AS L V I T D L T 0.210 6 L L V L I S I C W 0.210 199 R G G L D W C N A0.200 48 K V F S H R G G N 0.200 320 R P R R R C S P T 0.200 115 K G G SD S D A S 0.200 78 R I K W T K L T S 0.200 36 N G P H L L V E A 0.198345 Y G V Y C F R A Y 0.180 129 L T L E D Y G R Y 0.180 v.2-A24-9mers:151P3D4 176 K Y Q A V T A T L 840.000 195 H Y R K N K Q L M 30.000 132 HF Q V P S R I F 15.000 400 K A E N G P H L L 12.000 360 W Y V E N G R PA 9.000 81 K Q R K D K V L L 8.000 30 K Q D K K V D L L 8.000 8 T F P LR A L H I 7.500 382 A I E S L E E G L 7.200 279 A S P A A W L P L 6.000321 H S P S G G G G L 6.000 374 G Y C G A L W K A 5.500 104 S G S F C RN K L 5.280 66 A Y S N D G E H W 5.000 336 C Q G Q K H N V L 4.800 308 SP Y G P R N P L 4.800 57 V Q F V G S Y K L 4.400 99 E G I N I S G S F4.200 107 F C R N K L K Y L 4.000 234 F I F K T I A P L 4.000 378 A L WK A I E S L 4.000 109 R N K L K Y L A F 4.000 299 T S S S T Y D S L4.000 371 A G S G Y C G A L 4.000 262 S S A H R P P A L 4.000 1 M L E HT T K T F 3.000 226 G G S P R G L G F 2.400 228 S P R G L G F I F 2.40046 I I T Q G A K D F 2.000 125 N P S R R P Y H F 2.000 231 G L G F I F KT I 1.680 113 K Y L A F L H K R 1.650 227 G S P R G L G F I 1.500 38 L VP T K V T G I 1.500 93 A V V V S C E G I 1.500 39 V P T K V T G I I1.400 13 A L H I V V E S I 1.400 375 Y C G A L W K A I 1.200 219 K Y T ES P G G G 1.200 197 R K N K Q L M R L 1.200 76 V Y Q D E K Q R K 1.08095 V V S C E G I N I 1.000 242 L A A T R A T R I 1.000 399 R K A E N G PH L 0.960 58 Q F V G S Y K L A 0.750 116 A F L H K R M N T 0.750 29 M KQ D K K V D L 0.720 160 A Y K K V C L S G 0.700 235 I F K T I A P L A0.700 114 Y L A F L H K R M 0.600 362 V E N G R P A D L 0.600 110 N K LK Y L A F L 0.600 303 T Y D S L S P Y G 0.600 80 E K Q R K D K V L 0.600106 S F C R N K L K Y 0.550 205 L Q K Q A E K N M 0.500 62 S Y K L A Y SN D 0.500 12 R A L H I V V E S 0.462 3 E H T T K T F P L 0.400 158 S E AY K K V C L 0.400 277 P A A S P A A W L 0.400 224 P G G G S P R G L0.400 194 I H Y R K N K Q L 0.400 6 T K T F P L R A L 0.400 266 R P P AL S A R A 0.360 191 K A E I H Y R K N 0.330 204 R L Q K Q A E K N 0.330230 R G L G F I F K T 0.330 86 K V L L G R K A V 0.300 354 K S E N N S WY V 0.300 288 R T P W T R P S S 0.300 142 R Q E K A D G G S 0.300 237 KT I A P L A A T 0.300 256 R T P R A G S S A 0.300 393 K Q K D K E R K A0.264 352 K P K S E N N S W 0.240 138 R I F W R Q E K A 0.220 283 A W LP L R T P W 0.216 17 V V E S I R D H S 0.210 293 R P S S C P T S S 0.200249 R I G H P G G R T 0.200 51 A K D F G H V Q F 0.200 129 R P Y H F Q VP S 0.200 169 A P H E V G W K Y 0.185 316 L P N P R H S P S 0.180 67 Y SN D G E H W T 0.180 201 Q L M R L Q K Q A 0.180 133 F Q V P S R I F W0.180 123 N T N P S R R P Y 0.180 274 A P V P A A S P A 0.180 314 N P LP N P R H S 0.180 43 V T G I I T Q G A 0.168 152 C P Q G H A S E A 0.165356 E N N S W Y V E N 0.165 377 G A L W K A I E S 0.165 335 H C Q G Q KH N V 0.150 94 V V V S C E G I N 0.150 100 G I N I S G S F C 0.150 87 VL L G R K A V V 0.150 239 I A P L A A T R A 0.150

[0814] TABLE XIV Pos 1 2 3 4 5 6 7 8 9 0 Score Seq ID v.1-A24-10mers:151P3D4 136 R Y K C E V I E G L 560.000 271 T Y D E A V Q A C L 336.000261 F Y Y L I H P T K L 220.000 300 G Y D R C D A G W L 200.000 104 T YG G Y Q G R V F 100.000 133 D Y G R Y K C E V I 50.000 21 N Y T L D H DR A I 50.000 163 Y F P R L G R Y N L 30.000 173 N F H E A Q Q A C L24.000 247 R Y D V F C F T S N 12.000 87 D Y L K E V D V F V 10.500 252C F T S N F N G R F 10.000 115 K G G S D S D A S L 8.000 80 K W T K L TS D Y L 8.000 256 N F N G R F Y Y L I 7.500 262 Y Y L I H P T K L T7.500 158 G V V F P Y F P R L 7.200 185 D A V I A S F D Q L 7.200 344 LY G V Y C F R A Y 6.000 122 A S L V I T D L T L 6.000 63 F Y R D P T A FG S 6.000 31 H I Q A E N G P H L 6.000 290 G Q I F A A W K I L 6.000 237N Y G F W D K D K S 5.500 335 V G F P D K K H K L 5.280 155 D L Q G V VF P Y F 5.040 284 A Q I A K V G Q I F 5.040 99 G Y H K K T Y G G Y 5.00032 I Q A E N G P H L L 4.800 255 S N F N G R F Y Y L 4.800 193 Q L Y D AW R G G L 4.800 105 Y G G Y Q G R V F L 4.000 50 F S H R G G N V T L4.000 201 G L D W C N A G W L 4.000 9 L I S I C W A D H L 4.000 54 G G NV T L P C K F 3.960 152 V A L D L Q G V V F 3.600 41 L V E A E Q A K V F3.000 231 T V P G V R N Y G F 3.000 325 C S P T E A A V R F 3.000 3 S LL L L V L I S I 2.100 289 V G Q I F A A W K I 1.650 169 R Y N L N F H EA Q 1.500 283 G A Q I A K V G Q I 1.500 315 R Y P I S R P R R R 1.500309 L A D G S V R Y P I 1.400 210 L S D G S V Q Y P I 1.400 107 G Y Q GR V F L K G 1.386 68 T A F G S G I H K I 1.100 23 T L D H D R A I H I1.000 277 Q A C L N D G A Q I 1.000 117 G S D S D A S L V I 1.000 70 F GS G I H K I R I 1.000 179 Q A C L D Q D A V I 1.000 336 G F P D K K H KL Y 0.900 216 Q Y P I T K P R E P 0.825 162 P Y F P R L G R Y N 0.720145 L E D D T V V V A L 0.672 75 H K I R I K W T K L 0.660 239 G F W D KD K S R Y 0.600 49 V F S H R G G N V T 0.600 120 S D A S L V I T D L0.560 147 D D T V V V A L D L 0.560 182 L D Q D A V I A S F 0.504 194 LY D A W R G G L D 0.500 292 I F A A W K I L G Y 0.500 15 A D H L S D N YT L 0.400 341 K H K L Y G V Y C F 0.400 2 K S L L L L V L I S 0.360 245K S R Y D V F C F T 0.336 65 R D P T A F G S G I 0.300 297 K I L G Y D RC D A 0.300 248 Y D V F C F T S N F 0.300 328 T E A A V R F V G F 0.240221 K P R E P C G G Q N 0.240 72 S G I H K I R I K W 0.231 83 K L T S DY L K E V 0.220 177 A Q Q A C L D Q D A 0.216 140 E V I E G L E D D T0.216 5 L L L V L I S I C W 0.210 269 K L T Y D E A V Q A 0.200 61 C K FY R D P T A F 0.200 48 K V F S H R G G N V 0.200 343 K L Y G V Y C F R A0.200 103 K T Y G G Y Q G R V 0.200 76 K I R I K W T K L T 0.200 111 R VF L K G G S D S 0.200 244 D K S R Y D V F C F 0.200 242 D K D K S R Y DV F 0.200 86 S D Y L K E V D V F 0.200 130 T L E D Y G R Y K C 0.198 40L L V E A E Q A K V 0.198 180 A C L D Q D A V I A 0.180 278 A C L N D GA Q I A 0.180 275 A V Q A C L N D G A 0.180 4 L L L L V L I S I C 0.180143 E G L E D D T V V V 0.180 150 V V V A L D L Q G V 0.180 144 G L E DD T V V V A 0.180 200 G G L D W C N A G W 0.180 v.2-A24-10mers: 151P3D4113 K Y L A F L H K R M 90.000 374 G Y C G A L W K A I 60.000 233 G F IF K T I A P L 30.000 106 S F C R N K L K Y L 20.000 381 K A I E S L E EG L 17.280 219 K Y T E S P G G G S 12.000 109 R N K L K Y L A F L 8.00028 K M K Q D K K V D L 8.000 335 H C Q G Q K H N V L 7.200 307 L S P Y GP R N P L 7.200 130 P Y H F Q V P S R I 7.000 56 H V Q F V G S Y K L6.600 361 Y V E N G R P A D L 6.000 157 A S E A Y K K V C L 6.000 377 GA L W K A I E S L 6.000 103 I S G S F C R N K L 5.280 230 R G L G F I FK T I 5.040 160 A Y K K V C L S G A 5.000 66 A Y S N D G E H W T 5.000278 A A S P A A W L P L 4.800 12 R A L H I V V E S I 4.200 276 V P A A SP A A W L 4.000 261 G S S A H R P P A L 4.000 223 S P G G G S P R G L4.000 193 E I H Y R K N K Q L 4.000 370 L A G S G Y C G A L 4.000 5 T TK T F P L R A L 4.000 227 G S P R G L G F I F 3.600 124 T N P S R R P YH F 3.000 92 K A V V V S C E G I 3.000 45 G I I T Q G A K D F 3.000 50 GA K D F G H V Q F 2.400 7 K T F P L R A L H I 2.400 38 L V P T K V T G II 2.100 225 G G G S P R G L G F 2.000 37 L L V P T K V T G I 1.800 208 QA E K N M K K K I 1.650 94 V V V S C E G I N I 1.500 204 R L Q K Q A E KN M 1.500 176 K Y Q A V T A T L E 1.500 226 G G S P R G L G F I 1.200 76V Y Q D E K Q R K D 0.990 320 R H S P S G G G G L 0.960 399 R K A E N GP H L L 0.960 116 A F L H K R M N T N 0.900 360 W Y V E N G R P A D0.900 20 S I R D H S G Q K M 0.792 8 T F P L R A L H I V 0.750 132 H F QV P S R I F W 0.750 58 Q F V G S Y K L A Y 0.750 29 M K Q D K K V D L L0.720 80 E K Q R K D K V L L 0.600 53 D F G H V Q F V G S 0.600 309 P YG P R N P L P N 0.600 62 S Y K L A Y S N D G 0.600 175 W K Y Q A V T A TL 0.560 195 H Y R K N K Q L M R 0.500 303 T Y D S L S P Y G P 0.500 235I F K T I A P L A A 0.500 196 Y R K N K Q L M R L 0.400 398 E R K A E NG P H L 0.400 79 D E K Q R K D K V L 0.400 2 L E H T T K T F P L 0.400298 P T S S S T Y D S L 0.400 200 K Q L M R L Q K Q A 0.360 42 K V T G II T Q G A 0.336 211 K N M K K K I D K Y 0.330 348 K P Q R K P K S E N0.330 34 K V D L L V P T K V 0.308 273 R A P V P A A S P A 0.300 400 K AE N G P H L L V 0.300 142 R Q E K A D G G S C 0.300 313 R N P L P N P RH S 0.300 86 K V L L G R K A V V 0.300 288 R T P W T R P S S C 0.300 108C R N K L K Y L A F 0.300 98 C E G I N I S G S F 0.280 30 K Q D K K V DL L V 0.280 346 R G K P Q R K P K S 0.264 16 I V V E S I R D H S 0.252366 R P A D L A G S G Y 0.240 168 G A P H E V G W K Y 0.231 293 R P S SC P T S S S 0.200 131 Y H F Q V P S R I F 0.200 352 K P K S E N N S W Y0.200 183 T L E E K R K E K A 0.198 67 Y S N D G E H W T V 0.180 274 A PV P A A S P A A 0.180 283 A W L P L R T P W T 0.180 9 F P L R A L H I VV 0.180 101 I N I S G S F C R N 0.180 151 C C P Q G H A S E A 0.165 164V C L S G A P H E V 0.165 87 V L L G R K A V V V 0.150 305 D S L S P Y GP R N 0.150 97 S C E G I N I S G S 0.150 99 E G I N I S G S F C 0.150152 C P Q G H A S E A Y 0.150 327 G G L K K P A R H C 0.150 239 I A P LA A T R A T 0.150

[0815] TABLE XV Pos 1 2 3 4 5 6 7 8 9 Score Seq ID v.1-B7-9mers: 151P3D4164 F P R L G R Y N L 1200.000 186 A V I A S F D Q L 60.000 76 K I R I KW T K L 40.000 159 V V F P Y F P R L 20.000 320 R P R R R C S P T 20.000121 D A S L V I T D L 12.000 66 D P T A F G S G I 8.000 106 G G Y Q G RV F L 6.000 148 D T V V V A L D L 4.000 81 W T K L T S D Y L 4.000 51 SH R G G N V T L 4.000 134 Y G R Y K C E V I 4.000 116 G G S D S D A S L4.000 224 E P C G G Q N T V 4.000 123 S L V I T D L T L 4.000 10 I S I CW A D H L 4.000 291 Q I F A A W K I L 4.000 32 I Q A E N G P H L 4.000301 Y D R C D A G W L 4.000 33 Q A E N G P H L L 3.600 221 K P R E P C GG Q 3.000 331 A V R F V G F P D 1.500 180 A C L D Q D A V I 1.200 278 AC L N D G A Q I 1.200 284 A Q I A K V G Q I 1.200 151 V V A L D L Q G V1.000 313 S V R Y P I S R P 0.750 207 A G W L S D G S V 0.600 152 V A LD L Q G V V 0.600 179 Q A C L D Q D A V 0.600 306 A G W L A D G S V0.600 234 G V R N Y G F W D 0.500 7 L V L I S I C W A 0.500 161 F P Y FP R L G R 0.450 4 L L L L V L I S I 0.400 22 Y T L D H D R A I 0.400 137Y K C E V I E G L 0.400 256 N F N G R F Y Y L 0.400 202 L D W C N A G WL 0.400 326 S P T E A A V R F 0.400 71 G S G I H K I R I 0.400 16 D H LS D N Y T L 0.400 1 M K S L L L L V L 0.400 290 G Q I F A A W K I 0.400336 G F P D K K H K L 0.400 2 K S L L L L V L I 0.400 257 F N G R F Y YL I 0.400 262 Y Y L I H P T K L 0.400 232 V P G V R N Y G F 0.400 286 IA K V G Q I F A 0.300 41 L V E A E Q A K V 0.300 122 A S L V I T D L T0.300 189 A S F D Q L Y D A 0.300 318 I S R P R R R C S 0.300 197 A W RG G L D W C 0.300 96 V S M G Y H K K T 0.300 324 R C S P T E A A V 0.20088 Y L K E V D V F V 0.200 217 Y P I T K P R E P 0.200 316 Y P I S R P RR R 0.200 37 G P H L L V E A E 0.200 59 L P C K F Y R D P 0.200 245 K SR Y D V F C F 0.200 227 G G Q N T V P G V 0.200 266 H P T K L T Y D E0.200 84 L T S D Y L K E V 0.200 143 E G L E D D T V V 0.200 310 A D G SV R Y P I 0.180 194 L Y D A W R G G L 0.180 263 Y L I H P T K L T 0.150275 A V Q A C L N D G 0.150 298 I L G Y D R C D A 0.150 346 G V Y C F RA Y N 0.150 56 N V T L P C K F Y 0.150 48 K V F S H R G G N 0.150 69 A FG S G I H K I 0.120 337 F P D K K H K L Y 0.120 146 E D D T V V V A L0.120 174 F H E A Q Q A C L 0.120 272 Y D E A V Q A C L 0.120 249 D V FC F T S N F 0.100 172 L N F H E A Q Q A 0.100 322 R R R C S P T E A0.100 90 K E V D V F V S M 0.100 50 F S H R G G N V T 0.100 279 C L N DG A Q I A 0.100 26 H D R A I H I Q A 0.100 167 L G R Y N L N F H 0.100 5L L L V L I S I C 0.100 36 N G P H L L V E A 0.100 270 L T Y D E A V Q A0.100 178 Q Q A C L D Q D A 0.100 109 Q G R V F L K G G 0.100 199 R G GL D W C N A 0.100 288 K V G Q I F A A W 0.100 212 D G S V Q Y P I T0.100 258 N G R F Y Y L I H 0.100 39 H L L V E A E Q A 0.100 276 V Q A CL N D G A 0.100 53 R G G N V T L P C 0.100 v.2-B7-9mers: 151P3D4 308 S PY G P R N P L 180.000 81 K Q R K D K V L L 40.000 107 F C R N K L K Y L40.000 279 A S P A A W L P L 12.000 378 A L W K A I E S L 12.000 371 A GS G Y C G A L 12.000 39 V P T K V T G I I 8.000 240 A P L A A T R A T6.000 104 S G S F C R N K L 6.000 93 A V V V S C E G I 6.000 274 A P V PA A S P A 6.000 271 S A R A P V P A A 4.500 336 C Q G Q K H N V L 4.000299 T S S S T Y D S L 4.000 234 F I F K T I A P L 4.000 262 S S A H R PP A L 4.000 228 S P R G L G F I F 4.000 57 V Q F V G S Y K L 4.000 9 F PL R A L H I V 4.000 321 H S P S G G G G L 4.000 400 K A E N G P H L L3.600 382 A I E S L E E G L 3.600 311 G P R N P L P N P 3.000 38 L V P TK V T G I 2.000 318 N P R H S P S G G 2.000 95 V V S C E G I N I 2.000266 R P P A L S A R A 2.000 289 T P W T R P S S C 2.000 257 T P R A G SS A H 2.000 252 H P G G R T P R A 2.000 152 C P Q G H A S E A 2.000 277P A A S P A A W L 1.800 86 K V L L G R K A V 1.500 13 A L H I V V E S I1.200 169 A P H E V G W K Y 1.200 30 K Q D K K V D L L 1.200 242 L A A TR A T R I 1.200 291 W T R P S S C P T 1.000 114 Y L A F L H K R M 1.000205 L Q K Q A E K N M 1.000 195 H Y R K N K Q L M 1.000 172 E V G W K YQ A V 1.000 6 T K T F P L R A L 0.600 156 H A S E A Y K K V 0.600 264 AH R P P A L S A 0.450 254 G G R T P R A G S 0.450 244 A T R A T R I G H0.450 362 V E N G R P A D L 0.400 29 M K Q D K K V D L 0.400 3 E H T T KT F P L 0.400 316 L P N P R H S P S 0.400 129 R P Y H F Q V P S 0.400110 N K L K Y L A F L 0.400 186 E K R K E K A E I 0.400 125 N P S R R PY H F 0.400 375 Y C G A L W K A I 0.400 176 K Y Q A V T A T L 0.400 399R K A E N G P H L 0.400 227 G S P R G L G F I 0.400 293 R P S S C P T SS 0.400 276 V P A A S P A A W 0.400 352 K P K S E N N S W 0.400 231 G LG F I F K T I 0.400 80 E K Q R K D K V L 0.400 224 P G G G S P R G L0.400 314 N P L P N P R H S 0.400 197 R K N K Q L M R L 0.400 194 I H YR K N K Q L 0.400 158 S E A Y K K V C L 0.400 239 I A P L A A T R A0.300 247 A T R I G H P G G 0.300 344 L A R G K P Q R K 0.300 201 Q L MR L Q K Q A 0.300 370 L A G S G Y C G A 0.300 297 C P T S S S T Y D0.200 280 S P A A W L P L R 0.200 285 L P L R T P W T R 0.200 335 H C QG Q K H N V 0.200 366 R P A D L A G S G 0.200 49 Q G A K D F G H V 0.20089 L G R K A V V V S 0.200 322 S P S G G G G L K 0.200 127 S R R P Y H FQ V 0.200 88 L L G R K A V V V 0.200 135 V P S R I F W R Q 0.200 331 K PA R H C Q G Q 0.200 10 P L R A L H I V V 0.200 87 V L L G R K A V V0.200 348 K P Q R K P K S E 0.200 223 S P G G G S P R G 0.200 165 C L SG A P H E V 0.200 363 E N G R P A D L A 0.150 149 G S C C P Q G H A0.150 179 A V T A T L E E K 0.150 237 K T I A P L A A T 0.150 249 R I GH P G G R T 0.150 261 G S S A H R P P A 0.150 36 D L L V P T K V T 0.150328 G L K K P A R H C 0.150 282 A A W L P L R T P 0.135

[0816] TABLE XVI Pos 1 2 3 4 5 6 7 8 9 0 Score Seq ID v.1-B7-10mers:151P3D4 158 G V V F P Y F P R L 20.000 185 D A V I A S F D Q L 12.000122 A S L V I T D L T L 12.000 105 Y G G Y Q G R V F L 6.000 193 Q L Y DA W R G G L 6.000 316 Y P I S R P R R R C 4.500 217 Y P I T K P R E P C4.500 335 V G F P D K K H K L 4.000 9 L I S I C W A D H L 4.000 255 S NF N G R F Y Y L 4.000 32 I Q A E N G P H L L 4.000 221 K P R E P C G G QN 4.000 50 F S H R G G N V T L 4.000 290 G Q I F A A W K I L 4.000 115 KG G S D S D A S L 4.000 164 F P R L G R Y N L N 4.000 31 H I Q A E N G PH L 4.000 326 S P T E A A V R F V 4.000 59 L P C K F Y R D P T 3.000 320R P R R R C S P T E 2.000 266 H P T K L T Y D E A 2.000 331 A V R F V GF P D K 1.500 275 A V Q A C L N D G A 1.500 179 Q A C L D Q D A V I1.200 15 A D H L S D N Y T L 1.200 277 Q A C L N D G A Q I 1.200 283 G AQ I A K V G Q I 1.200 201 G L D W C N A G W L 1.200 68 T A F G S G I H KI 1.200 48 K V F S H R G G N V 1.000 151 V V A L D L Q G V V 1.000 150 VV V A L D L Q G V 1.000 245 K S R Y D V F C F T 1.000 76 K I R I K W T KL T 1.000 305 D A G W L A D G S V 0.600 206 N A G W L S D G S V 0.600163 Y F P R L G R Y N L 0.600 309 L A D G S V R Y P I 0.540 234 G V R NY G F W D K 0.500 140 E V I E G L E D D T 0.500 95 F V S M G Y H K K T0.500 313 S V R Y P I S R P R 0.500 70 F G S G I H K I R I 0.400 161 F PY F P R L G R Y 0.400 136 R Y K C E V I E G L 0.400 147 D D T V V V A LD L 0.400 173 N F H E A Q Q A C L 0.400 232 V P G V R N Y G F W 0.400289 V G Q I F A A W K I 0.400 75 H K I R I K W T K L 0.400 261 F Y Y L IH P T K L 0.400 3 S L L L L V L I S I 0.400 120 S D A S L V I T D L0.400 80 K W T K L T S D Y L 0.400 286 I A K V G Q I F A A 0.300 121 D AS L V I T D L T 0.300 186 A V I A S F D Q L Y 0.300 188 I A S F D Q L YD A 0.300 180 A C L D Q D A V I A 0.300 196 D A W R G G L D W C 0.300177 A Q Q A C L D Q D A 0.300 278 A C L N D G A Q I A 0.300 33 Q A E N GP H L L V 0.270 66 D P T A F G S G I H 0.200 226 C G G Q N T V P G V0.200 224 E P C G G Q N T V P 0.200 116 G G S D S D A S L V 0.200 109 QG R V F L K G G S 0.200 37 G P H L L V E A E Q 0.200 178 Q Q A C L D Q DA V 0.200 143 E G L E D D T V V V 0.200 103 K T Y G G Y Q G R V 0.200 40L L V E A E Q A K V 0.200 83 K L T S D Y L K E V 0.200 297 K I L G Y D RC D A 0.150 318 I S R P R R R C S P 0.150 322 R R R C S P T E A A 0.150271 T Y D E A V Q A C L 0.120 145 L E D D T V V V A L 0.120 117 G S D SD A S L V I 0.120 210 L S D G S V Q Y P I 0.120 300 G Y D R C D A G W L0.120 23 T L D H D R A I H I 0.120 167 L G R Y N L N F H E 0.100 249 D VF C F T S N F N 0.100 269 K L T Y D E A V Q A 0.100 73 G I H K I R I K WT 0.100 6 L L V L I S I C W A 0.100 35 E N G P H L L V E A 0.100 20 D NY T L D H D R A 0.100 270 L T Y D E A V Q A C 0.100 285 Q I A K V G Q IF A 0.100 111 R V F L K G G S D S 0.100 172 L N F H E A Q Q A C 0.100171 N L N F H E A Q Q A 0.100 134 Y G R Y K C E V I E 0.100 113 F L K GG S D S D A 0.100 343 K L Y G V Y C F R A 0.100 4 L L L L V L I S I C0.100 231 T V P G V R N Y G F 0.100 v.2-B7-10mers: 151P3D4 276 V P A A SP A A W L 120.000 223 S P G G G S P R G L 80.000 278 A A S P A A W L P L36.000 56 H V Q F V G S Y K L 20.000 377 G A L W K A I E S L 12.000 370L A G S G Y C G A L 12.000 381 K A I E S L E E G L 12.000 20 S I R D H SG Q K M 10.000 307 L S P Y G P R N P L 9.000 5 T T K T F P L R A L 6.000361 Y V E N G R P A D L 6.000 103 I S G S F C R N K L 6.000 274 A P V PA A S P A A 6.000 109 R N K L K Y L A F L 4.000 335 H C Q G Q K H N V L4.000 261 G S S A H R P P A L 4.000 28 K M K Q D K K V D L 4.000 9 F P LR A L H I V V 4.000 193 E I H Y R K N K Q L 4.000 157 A S E A Y K K V CL 3.600 318 N P R H S P S G G G 3.000 39 V P T K V T G I I T 2.000 94 VV V S C E G I N I 2.000 228 S P R G L G F I F K 2.000 311 G P R N P L PN P R 2.000 38 L V P T K V T G I I 2.000 257 T P R A G S S A H R 2.000280 S P A A W L P L R T 2.000 92 K A V V V S C E G I 1.200 12 R A L H IV V E S I 1.200 89 L G R K A V V V S C 1.000 107 F C R N K L K Y L A1.000 204 R L Q K Q A E K N M 1.000 86 K V L L G R K A V V 1.000 240 A PL A A T R A T R 0.900 169 A P H E V G W K Y Q 0.600 348 K P Q R K P K SE N 0.600 267 P P A L S A R A P V 0.600 293 R P S S C P T S S S 0.600271 S A R A P V P A A S 0.600 42 K V T G I I T Q G A 0.500 172 E V G W KY Q A V T 0.500 115 L A F L H K R M N T 0.450 260 A G S S A H R P P A0.450 263 S A H R P P A L S A 0.450 344 L A R G K P Q R K P 0.450 314 NP L P N P R H S P 0.450 226 G G S P R G L G F I 0.400 106 S F C R N K LK Y L 0.400 398 E R K A E N G P H L 0.400 366 R P A D L A G S G Y 0.4002 L E H T T K T F P L 0.400 175 W K Y Q A V T A T L 0.400 152 C P Q G HA S E A Y 0.400 79 D E K Q R K D K V L 0.400 399 R K A E N G P H L L0.400 320 R H S P S G G G G L 0.400 297 C P T S S S T Y D S 0.400 298 PT S S S T Y D S L 0.400 233 G F I F K T I A P L 0.400 196 Y R K N K Q LM R L 0.400 230 R G L G F I F K T I 0.400 7 K T F P L R A L H I 0.400 80E K Q R K D K V L L 0.400 352 K P K S E N N S W Y 0.400 29 M K Q D K K VD L L 0.400 37 L L V P T K V T G I 0.400 208 Q A E K N M K K K I 0.360239 I A P L A A T R A T 0.300 34 K V D L L V P T K V 0.300 289 T P W T RP S S C P 0.300 125 N P S R R P Y H F Q 0.300 156 H A S E A Y K K V C0.300 247 A T R I G H P G G R 0.300 244 A T R A T R I G H P 0.300 269 AL S A R A P V P A 0.300 285 L P L R T P W T R P 0.300 93 A V V V S C E GI N 0.300 273 R A P V P A A S P A 0.300 282 A A W L P L R T P W 0.270400 K A E N G P H L L V 0.270 291 W T R P S S C P T S 0.200 26 G Q K M KQ D K K V 0.200 164 V C L S G A P H E V 0.200 252 H P G G R T P R A G0.200 322 S P S G G G G L K K 0.200 308 S P Y G P R N P L P 0.200 87 V LL G R K A V V V 0.200 67 Y S N D G E H W T V 0.200 129 R P Y H F Q V P SR 0.200 331 K P A R H C Q G Q K 0.200 254 G G R T P R A G S S 0.200 126P S R R P Y H F Q V 0.200 364 N G R P A D L A G S 0.200 266 R P P A L SA R A P 0.200 48 T Q G A K D F G H V 0.200 316 L P N P R H S P S G 0.200135 V P S R I F W R Q E 0.200 179 A V T A T L E E K R 0.150 327 G G L KK P A R H C 0.150

[0817] TABLE XVII Pos 1 2 3 4 5 6 7 8 9 Score Seq ID v.1-B35-9mers:151P3D4 164 F P R L G R Y N L 60.000 245 K S R Y D V F C F 45.000 326 SP T E A A V R F 40.000 232 V P G V R N Y G F 20.000 320 R P R R R C S PT 12.000 337 F P D K K H K L Y 12.000 254 T S N F N G R F Y 10.000 66 DP T A F G S G I 8.000 76 K I R I K W T K L 6.000 293 F A A W K I L G Y6.000 129 L T L E D Y G R Y 6.000 10 I S I C W A D H L 5.000 209 W L S DG S V Q Y 4.000 308 W L A D G S V R Y 4.000 224 E P C G G Q N T V 4.0002 K S L L L L V L I 4.000 81 W T K L T S D Y L 3.000 121 D A S L V I T DL 3.000 329 E A A V R F V G F 3.000 221 K P R E P C G G Q 2.400 187 V IA S F D Q L Y 2.000 230 N T V P G V R N Y 2.000 255 S N F N G R F Y Y2.000 71 G S G I H K I R I 2.000 345 Y G V Y C F R A Y 2.000 166 R L G RY N L N F 2.000 116 G G S D S D A S L 2.000 264 L I H P T K L T Y 2.00097 S M G Y H K K T Y 2.000 56 N V T L P C K F Y 2.000 155 D L Q G V V FP Y 2.000 32 I Q A E N G P H L 2.000 14 W A D H L S D N Y 1.800 196 D AW R G G L D W 1.500 318 I S R P R R R C S 1.500 134 Y G R Y K C E V I1.200 88 Y L K E V D V F V 1.200 152 V A L D L Q G V V 1.200 106 G G Y QG R V F L 1.000 148 D T V V V A L D L 1.000 189 A S F D Q L Y D A 1.000186 A V I A S F D Q L 1.000 253 F T S N F N G R F 1.000 123 S L V I T DL T L 1.000 55 G N V T L P C K F 1.000 159 V V F P Y F P R L 1.000 285 QI A K V G Q I F 1.000 156 L Q G V V F P Y F 1.000 249 D V F C F T S N F1.000 291 Q I F A A W K I L 1.000 105 Y G G Y Q G R V F 1.000 288 K V GQ I F A A W 1.000 179 Q A C L D Q D A V 0.900 286 I A K V G Q I F A0.900 33 Q A E N G P H L L 0.900 90 K E V D V F V S M 0.800 22 Y T L D HD R A I 0.800 180 A C L D Q D A V I 0.800 278 A C L N D G A Q I 0.600243 K D K S R Y D V F 0.600 100 Y H K K T Y G G Y 0.600 78 R I K W T K LT S 0.600 143 E G L E D D T V V 0.600 28 R A I H I Q A E N 0.600 126 I TD L T L E D Y 0.600 96 V S M G Y H K K T 0.500 122 A S L V I T D L T0.500 6 L L V L I S I C W 0.500 50 F S H R G G N V T 0.500 73 G I H K IR I K W 0.500 301 Y D R C D A G W L 0.450 117 G S D S D A S L V 0.450 84L T S D Y L K E V 0.400 80 K W T K L T S D Y 0.400 284 A Q I A K V G Q I0.400 324 R C S P T E A A V 0.400 257 F N G R F Y Y L I 0.400 4 L L L LV L I S I 0.400 290 G Q I F A A W K I 0.400 340 K K H K L Y G V Y 0.400153 A L D L Q G V V F 0.300 305 D A G W L A D G S 0.300 199 R G G L D WC N A 0.300 115 K G G S D S D A S 0.300 151 V V A L D L Q G V 0.300 51 SH R G G N V T L 0.300 206 N A G W L S D G S 0.300 62 K F Y R D P T A F0.300 183 D Q D A V I A S F 0.300 270 L T Y D E A V Q A 0.300 42 V E A EQ A K V F 0.200 53 R G G N V T L P C 0.200 59 L P C K F Y R D P 0.200306 A G W L A D G S V 0.200 137 Y K C E V I E G L 0.200 227 G G Q N T VP G V 0.200 37 G P H L L V E A E 0.200 161 F P Y F P R L G R 0.200 336 GF P D K K H K L 0.200 48 K V F S H R G G N 0.200 v.2-B35-9mers: 151P3D4352 K P K S E N N S w 90.000 169 A P H E V G W K Y 80.000 228 S P R G LG F I F 60.000 308 S P Y G P R N P L 20.000 125 N P S R R P Y H F 20.000276 V P A A S P A A W 10.000 81 K Q R K D K V L L 9.000 39 V P T K V T GI I 8.000 205 L Q K Q A E K N M 6.000 212 N M K K K I D K Y 6.000 109 RN K L K Y L A F 6.000 299 T S S S T Y D S L 5.000 262 S S A H R P P A L5.000 321 H S P S G G G G L 5.000 279 A S P A A W L P L 5.000 302 S T YD S L S P Y 4.000 129 R P Y H F Q V P S 4.000 266 R P P A L S A R A4.000 9 F P L R A L H I V 4.000 293 R P S S C P T S S 4.000 107 F C R NK L K Y L 3.000 372 G S G Y C G A L W 2.500 316 L P N P R H S P S 2.000274 A P V P A A S P A 2.000 152 C P Q G H A S E A 2.000 252 H P G G R TP R A 2.000 296 S C P T S S S T Y 2.000 240 A P L A A T R A T 2.000 114Y L A F L H K R M 2.000 227 G S P R G L G F I 2.000 123 N T N P S R R PY 2.000 59 F V G S Y K L A Y 2.000 289 T P W T R P S S C 2.000 314 N P LP N P R H S 2.000 400 K A E N G P H L L 1.800 242 L A A T R A T R I1.200 393 K Q K D K E R K A 1.200 156 H A S E A Y K K V 1.200 371 A G SG Y C G A L 1.000 99 E G I N I S G S F 1.000 336 C Q G Q K H N V L 1.000104 S G S F C R N K L 1.000 234 F I F K T I A P L 1.000 378 A L W K A IE S L 1.000 57 V Q F V G S Y K L 1.000 46 I I T Q G A K D F 1.000 226 GG S P R G L G F 1.000 96 V S C E G I N I S 1.000 67 Y S N D G E H W T1.000 271 S A R A P V P A A 0.900 366 R P A D L A G S G 0.800 257 T P RA G S S A H 0.600 318 N P R H S P S G G 0.600 195 H Y R K N K Q L M0.600 95 V V S C E G I N I 0.600 12 R A L H I V V E S 0.600 354 K S E NN S W Y V 0.600 311 G P R N P L P N P 0.600 30 K Q D K K V D L L 0.600261 G S S A H R P P A 0.500 300 S S S T Y D S L S 0.500 270 L S A R A PV P A 0.500 167 S G A P H E V G W 0.500 295 S S C P T S S S T 0.500 149G S C C P Q G H A 0.500 61 G S Y K L A Y S N 0.500 133 F Q V P S R I F W0.500 69 N D G E H W T V Y 0.400 13 A L H I V V E S I 0.400 231 G L G FI F K T I 0.400 38 L V P T K V T G I 0.400 375 Y C G A L W K A I 0.400348 K P Q R K P K S E 0.400 86 K V L L G R K A V 0.400 93 A V V V S C EG I 0.400 399 R K A E N G P H L 0.400 331 K P A R H C Q G Q 0.400 328 GL K K P A R H C 0.300 277 P A A S P A A W L 0.300 239 I A P L A A T R A0.300 89 L G R K A V V V S 0.300 49 Q G A K D F G H V 0.300 382 A I E SL E E G L 0.300 254 G G R T P R A G S 0.300 291 W T R P S S C P T 0.300377 G A L W K A I E S 0.300 263 S A H R P P A L S 0.300 159 E A Y K K VC L S 0.300 1 M L E H T T K T F 0.300 370 L A G S G Y C G A 0.300 115 LA F L H K R M N 0.300 5 T T K T F P L R A 0.300 230 R G L G F I F K T0.200 280 S P A A W L P L R 0.200 138 R I F W R Q E K A 0.200 322 S P SG G G G L K 0.200 288 R T P W T R P S S 0.200 297 C P T S S S T Y D0.200 249 R I G H P G G R T 0.200 204 R L Q K Q A E K N 0.200

[0818] TABLE XVIII Pos 1 2 3 4 5 6 7 8 9 0 Score Seq ID v.1-B35-10mers:151P3D4 161 F P Y F P R L G R Y 40.000 221 K P R E P C G G Q N 24.000254 T S N F N G R F Y Y 10.000 96 V S M G Y H K K T Y 10.000 232 V P G VR N Y G F W 10.000 326 S P T E A A V R F V 8.000 164 F P R L G R Y N L N6.000 152 V A L D L Q G V V F 6.000 122 A S L V I T D L T L 5.000 325 CS P T E A A V R F 5.000 189 A S F D Q L Y D A W 5.000 50 F S H R G G N VT L 5.000 125 V I T D L T L E D Y 4.000 185 D A V I A S F D Q L 3.000128 D L T L E D Y G R Y 3.000 245 K S R Y D V F C F T 3.000 55 G N V T LP C K F Y 2.000 115 K G G S D S D A S L 2.000 59 L P C K F Y R D P T2.000 217 Y P I T K P R E P C 2.000 229 Q N T V P G V R N Y 2.000 253 FT S N F N G R F Y 2.000 32 I Q A E N G P H L L 2.000 193 Q L Y D A W R GG L 2.000 263 Y L I H P T K L T Y 2.000 186 A V I A S F D Q L Y 2.000316 Y P I S R P R R R C 2.000 266 H P T K L T Y D E A 2.000 277 Q A C LN D G A Q I 1.800 68 T A F G S G I H K I 1.200 179 Q A C L D Q D A V I1.200 283 G A Q I A K V G Q I 1.200 320 R P R R R C S P T E 1.200 284 AQ I A K V G Q I F 1.000 335 V G F P D K K H K L 1.000 299 L G Y D R C DA G W 1.000 105 Y G G Y Q G R V F L 1.000 290 G Q I F A A W K I L 1.000255 S N F N G R F Y Y L 1.000 158 G V V F P Y F P R L 1.000 231 T V P GV R N Y G F 1.000 2 K S L L L L V L I S 1.000 200 G G L D W C N A G W1.000 31 H I Q A E N G P H L 1.000 54 G G N V T L P C K F 1.000 9 L I SI C W A D H L 1.000 155 D L Q G V V F P Y F 1.000 88 Y L K E V D V F V S0.900 286 I A K V G Q I F A A 0.900 91 E V D V F V S M G Y 0.600 210 L SD G S V Q Y P I 0.600 305 D A G W L A D G S V 0.600 136 R Y K C E V I EG L 0.600 206 N A G W L S D G S V 0.600 117 G S D S D A S L V I 0.600339 D K K H K L Y G V Y 0.600 143 E G L E D D T V V V 0.600 116 G G S DS D A S L V 0.600 239 G F W D K D K S R Y 0.600 76 K I R I K W T K L T0.600 341 K H K L Y G V Y C F 0.600 40 L L V E A E Q A K V 0.600 10 I SI C W A D H L S 0.500 5 L L L V L I S I C W 0.500 72 S G I H K I R I K W0.500 103 K T Y G G Y Q G R V 0.400 336 G F P D K K H K L Y 0.400 13 C WA D H L S D N Y 0.400 48 K V F S H R G G N V 0.400 3 S L L L L V L I S I0.400 289 V G Q I F A A W K I 0.400 70 F G S G I H K I R I 0.400 83 K LT S D Y L K E V 0.400 309 L A D G S V R Y P I 0.360 297 K I L G Y D R CD A 0.300 109 Q G R V F L K G G S 0.300 269 K L T Y D E A V Q A 0.300180 A C L D Q D A V I A 0.300 201 G L D W C N A G W L 0.300 121 D A S LV I T D L T 0.300 41 L V E A E Q A K V F 0.300 196 D A W R G G L D W C0.300 188 I A S F D Q L Y D A 0.300 150 V V V A L D L Q G V 0.300 178 QQ A C L D Q D A V 0.300 113 F L K G G S D S D A 0.300 85 T S D Y L K E VD V 0.300 111 R V F L K G G S D S 0.200 151 V V A L D L Q G V V 0.200344 L Y G V Y C F R A Y 0.200 343 K L Y G V Y C F R A 0.200 307 G W L AD G S V R Y 0.200 292 I F A A W K I L G Y 0.200 80 K W T K L T S D Y L0.200 182 L D Q D A V I A S F 0.200 66 D P T A F G S G I H 0.200 270 L TY D E A V Q A C 0.200 99 G Y H K K T Y G G Y 0.200 226 C G G Q N T V P GV 0.200 224 E P C G G Q N T V P 0.200 v.2-B35-10mers: 151P3D4 352 K P KS E N N S W Y 240.000 366 R P A D L A G S G Y 160.000 152 C P Q G H A SE A Y 40.000 276 V P A A S P A A W L 20.000 223 S P G G G S P R G L20.000 50 G A K D F G H V Q F 18.000 20 S I R D H S G Q K M 12.000 381 KA I E S L E E G L 12.000 301 S S T Y D S L S P Y 10.000 105 G S F C R NK L K Y 10.000 295 S S C P T S S S T Y 10.000 109 R N K L K Y L A F L6.000 168 G A P H E V G W K Y 6.000 28 K M K Q D K K V D L 6.000 227 G SP R G L G F I F 5.000 261 G S S A H R P P A L 5.000 307 L S P Y G P R NP L 5.000 103 I S G S F C R N K L 5.000 348 K P Q R K P K S E N 4.000 9F P L R A L H I V V 4.000 211 K N M K K K I D K Y 4.000 293 R P S S C PT S S S 4.000 204 R L Q K Q A E K N M 4.000 67 Y S N D G E H W T V 3.000370 L A G S G Y C G A L 3.000 278 A A S P A A W L P L 3.000 377 G A L WK A I E S L 3.000 5 T T K T F P L R A L 3.000 166 L S G A F H E V G W2.500 187 K R K E K A E I H Y 2.400 12 R A L H I V V E S I 2.400 92 K AV V V S C E G I 2.400 65 L A Y S N D G E H W 2.250 39 V P T K V T G I IT 2.000 297 C P T S S S T Y D S 2.000 280 S P A A W L P L R T 2.000 274A P V P A A S P A A 2.000 54 F G H V Q F V G S Y 2.000 122 M N T N P S RR P Y 2.000 282 A A W L P L R T P W 1.500 157 A S E A Y K K V C L 1.50056 H V Q F V G S Y K L 1.000 193 E I H Y R K N K Q L 1.000 45 G I I T QG A K D F 1.000 225 G G G S P R G L G F 1.000 335 H C Q G Q K H N V L1.000 124 T N P S R R P Y H F 1.000 271 S A R A P V P A A S 0.900 7 K TF P L R A L H I 0.800 230 R G L G F I F K T I 0.800 68 S N D G E H W T VY 0.600 311 G P R N P L P N P R 0.600 94 V V V S C E G I N I 0.600 273 RA P V P A A S P A 0.600 228 S P R G L G F I F K 0.600 156 H A S E A Y KK V C 0.600 257 T P R A G S S A H R 0.600 346 R G K P Q R K P K S 0.60026 G Q K M K Q D K K V 0.600 318 N P R H S P S G G G 0.600 371 A G S G YC G A L W 0.500 299 T S S S T Y D S L S 0.500 149 G S C C P Q G H A S0.500 305 D S L S P Y G P R N 0.500 270 L S A R A P V P A A 0.500 262 SS A H R P P A L S 0.500 364 N G R P A D L A G S 0.450 86 K V L L G R K AV V 0.400 399 R K A E N G P H L L 0.400 226 G G S P R G L G F I 0.400266 R P P A L S A R A P 0.400 37 L L V P T K V T G I 0.400 129 R P Y H FQ V P S R 0.400 113 K Y L A F L H K R M 0.400 169 A P H E V G W K Y Q0.400 38 L V P T K V T G I I 0.400 267 P P A L S A R A P V 0.400 331 K PA R H C Q G Q K 0.400 208 Q A E K N M K K K I 0.360 400 K A E N G P H LL V 0.360 79 D E K Q R K D K V L 0.300 107 F C R N K L K Y L A 0.300 115L A F L H K R M N T 0.300 398 E R K A E N G P H L 0.300 239 I A P L A AT R A T 0.300 361 Y V E N G R P A D L 0.300 291 W T R P S S C P T S0.300 263 S A H R P P A L S A 0.300 212 N M K K K I D K Y T 0.300 196 YR K N K Q L M R L 0.300 254 G G R T P R A G S S 0.300 126 P S R R P Y HF Q V 0.300 89 L G R K A V V V S C 0.300 48 T Q G A K D F G H V 0.300314 N P L P N P R H S P 0.200 194 I H Y R K N K Q L M 0.200 322 S P S GG G G L K K 0.200 164 V C L S G A P H E V 0.200 288 R T P W T R P S S C0.200 42 K V T G I I T Q G A 0.200

[0819] TABLE XIX Frequently Occurring Motifs avrg. % Name identityDescription Potential Function zf-C2H2 34% Zinc finger, C2H2 typeNucleic acid-binding protein functions as transcription factor, nuclearlocation probable cytochrome_b_N 68% Cytochrome b(N- membrane boundoxidase, generate terminal)/b6/petB superoxide ig 19% Immunoglobulindomain domains are one hundred amino acids long and include a conservedintradomain disulfide bond. WD40 18% WD domain, G-beta tandem repeats ofabout 40 repeat residues, each containing a Trp-Asp motif. Function insignal transduction and protein interaction PDZ 23% PDZ domain mayfunction in targeting signaling molecules to sub-membranous sites LRR28% Leucine Rich Repeat short sequence motifs involved inprotein-protein interactions pkinase 23% Protein kinase domain conservedcatalytic core common to both serine/threonine and tyrosine proteinkinases containing an ATP binding site and a catalytic site PH 16% PHdomain pleckstrin homology involved in intracellular signaling or asconstituents of the cytoskeleton EGF 34% EGF-like domain 30-40amino-acid long found in the extracellular domain of membrane- boundproteins or in secreted proteins rvt 49% Reverse transcriptase(RNA-dependent DNA polymerase) ank 25% Ank repeat Cytoplasmic protein,associates integral membrane proteins to the cytoskeleton oxidored_q132% NADH- membrane associated. Involved in Ubiquinone/plastoquinoneproton translocation across the (complex I), various membrane chainsefhand 24% EF hand calcium-binding domain, consists of a12 residue loopflanked on both sides by a 12 residue alpha-helical domain rvp 79%Retroviral aspartyl Aspartyl or acid proteases, centered protease on acatalytic aspartyl residue Collagen 42% Collagen triple helixextracellular structural proteins repeat (20 copies) involved information of connective tissue. The sequence consists of the G-X-Y andthe polypeptide chains forms a triple helix. fn3 20% Fibronectin typeIII Located in the extracellular ligand- domain binding region ofreceptors and is about 200 amino acid residues long with two pairs ofcysteines involved in disulfide bonds 7tm_1 19% 7 transmembrane sevenhydrophobic transmembrane receptor (rhodopsin regions, with theN-terminus family) located extracellularly while the C- terminus iscytoplasmic. Signal through G proteins

[0820] TABLE XX Motifs and Post-translational Modifications of 151P3D4N-glycosylation site. 21-24 NYTL 56-59 NVTL cAMP- and cGMP-dependentprotein kinase phosphorylation site 323-326 RRcS Protein kinase Cphosphorylation site 51-53 ShR 313-315 SvR Casein kinase IIphosphorylation site 118-121 SdsD 130-133 TleD 246-249 SryD 271-274 TydE326-329 SptE N-myristoylation site 54-59 GGnvTL 106-111 GGyqGR 116-121GGsdSD 201-206 GLdwCN 227-232 GGqnTV 283-288 GAqiAK 290-295 GQifAA

[0821] TABLE XXI Protein Properties of 151P3D4 Bioinformatic Program URLOutcome 151P3D4 V.1 ORF ORF finder bp316-1380 (includes stop) Proteinlength 354 aa Transmembrane TM Pred http://www.ch.embnet.org/ no TMregion HMMTop http://www.enzim.hu/hmmtop/ no TM, intracellular Sosuihttp://www.genome.ad.jp/SOSui/ no TM, soluble protein TMHMMhttp://www.cbs.dtu.dk/services/TMHMM no TM Signal Peptide Signal Phttp://www.cbs.dtu.dk/services/SignalP/ yes pI pI/MW toolhttp://www.expasy.ch/tools/ 7.1 Molecular weight pI/MW toolhttp://www.expasy.ch/tools/ 40.1 kDa Localization PSORThttp://psort.nibb.ac.jp/ 53% outside, 51% lysosome PSORT IIhttp://psort.nibb.ac.jp/ 66% extracellular, 11% cytoplasmic Motifs Pfamhttp://www.sanger.ac.uk/Pfam/ Ig domain, extracellular link domainPrints http://www.biochem.ucl.ac.uk/ Link module Blockshttp://www.blocks.fhcrc.org/ Link motif, C-type lectin domain, receptortyrosine kinase class III 151P3D4 V.2 ORF ORF finder bp1-2166 (includesstop) Protein length 721 aa Transmembrane TM Predhttp://www.ch.embnet.org/ no TM region HMMTophttp://www.enzim.hu/hmmtop/ no TM, extracellular Sosuihttp://www.genome.ad.jp/SOSui/ no TM, soluble protein TMHMMhttp://www.cbs.dtu.dk/services/TMHMM no TM Signal Peptide Signal Phttp://www.cbs.dtu.dk/services/SignalP/ none pI pI/MW toolhttp://www.expasy.ch/tools/ pI9.6 Molecular weight pI/MW toolhttp://www.expasy.ch/tools/ 80.7 kDa Localization PSORThttp://psort.nibb.ac.jp/ 82% nucleus, 42% peroxisome PSORT IIhttp://psort.nibb.ac.jp/ 52% nuclear, 26% cytoplasmic Motifs Pfamhttp://www.sanger.ac.uk/Pfam/ F5/8 type C domain, Ig domainextracellular link domain Prints http://www.biochem.ucl.ac.uk/ linkmodule signature Blocks http://www.blocks.fhcrc.org/ Link motif,coagulation factor 5/8 type c domain (FA58C), ribosomal protein L13,C-type lectin domain, receptor tyrosine kinase class III

[0822] TABLE XXII SEQ. Pos 1 2 3 4 5 6 7 8 9 score ID NO. 151P3D4 v.1:HLA Peptide Scoring Results A1 9-mers SYFPEITHI 126 I T D L T L E D Y 31230 N T V P G V R N Y 28 337 F P D K K H K L Y 28 240 F W D K D K S R Y26 14 W A D H L S D N Y 25 264 L I H P T K L T Y 25 293 F A A W K I L GY 22 18 L S D N Y T L D H 21 129 L T L E D Y G R Y 21 155 D L Q G V V FP Y 20 254 T S N F N G R F Y 20 255 S N F N G R F Y Y 20 345 Y G V Y C FR A Y 20 162 P Y F P R L G R Y 19 92 V D V F V S M G Y 18 187 V I A S FD Q L Y 18 209 W L S D G S V Q Y 18 303 R C D A G W L A D 18 308 W L A DG S V R Y 18 97 S M G Y H K K T Y 17 100 Y H K K T Y G G Y 17 327 P T EA A V R F V 17 56 N V T L P C K F Y 16 64 Y R D P T A F G S 16 117 G S DS D A S L V 16 153 A L D L Q G V V F 16 210 L S D G S V Q Y P 16 340 K KH K L Y G V Y 16 80 K W T K L T S D Y 15 85 T S D Y L K E V D 15 108 Y QG R V F L K G 15 131 L E D Y G R Y K C 15 222 P R E P C G G Q N 15 280 LN D G A Q I A K 15 33 Q A E N G P H L L 14 119 D S D A S L V I T 14 148D T V V V A L D L 14 272 Y D E A V Q A C L 14 130 T L E D Y G R Y K 13146 E D D T V V V A L 13 174 F H E A Q Q A C L 13 23 T L D H D R A I H12 41 L V E A E Q A K V 12 89 L K E V D V F V S 12 91 E V D V F V S M G12 138 K C E V I E G L E 12 141 V I E G L E D D T 12 144 G L E D D T V VV 12 145 L E D D T V V V A 12 183 D Q D A V I A S F 12 190 S F D Q L Y DA W 12 201 G L D W C N A G W 12 309 L A D G S V R Y P 12 34 A E N G P HL L V 11 35 E N G P H L L V E 11 57 V T L P C K F Y R 11 181 C L D Q D AV I A 11 194 L Y D A W R G G L 11 242 D K D K S R Y D V 11 271 T Y D E AV Q A C 11 3 S L L L L V L I S 10 25 D H D R A I H I Q 10 43 E A E Q A KV F S 10 219 I T K P R E P C G 10 247 R Y D V F C F T S 10 300 G Y D R CD A G W 10 50 F S H R G G N V T 9 83 K L T S D Y L K E 9 96 V S M G Y HK K T 9 103 K T Y G G Y Q G R 9 118 S D S D A S L V I 9 123 S L V I T DL T L 9 159 V V F P Y F P R L 9 161 F P Y F P R L G R 9 166 R L G R Y NL N F 9 196 D A W R G G L D W 9 213 G S V Q Y P I T K 9 312 G S V R Y PI S R 9 318 I S R P R R R C S 9 22 Y T L D H D R A I 8 53 R G G N V T LP C 8 67 P T A F G S G I H 8 71 G S G I H K I R I 8 204 W C N A G W L SD 8 253 F T S N F N G R F 8 1 M K S L L L L V L 7 4 L L L L V L I S I 773 G I H K I R I K W 7 84 L T S D Y L K E V 7 120 S D A S L V I T D 7122 A S L V I T D L T 7 125 V I T D L T L E D 7 139 C E V I E G L E D 7150 V V V A L D L Q G 7 189 A S F D Q L Y D A 7 246 S R Y D V F C F T 7258 N G R F Y Y L I H 7 2 K S L L L L V L I 6 12 I C W A D H L S D 6 51S H R G G N V T L 6 68 T A F G S G I H K 6 78 R I K W T K L T S 6 81 W TK L T S D Y L 6 105 Y G G Y Q G R V F 6 176 E A Q Q A C L D Q 6 188 I AS F D Q L Y D 6 235 V R N Y G F W D K 6 263 Y L I H P T K L T 6 267 P TK L T Y D E A 6 270 L T Y D E A V Q A 6 274 E A V Q A C L N D 6 286 I AK V G Q I F A 6 292 I F A A W K I L G 6 332 V R F V G F P D K 6 338 P DK K H K L Y G 6 6 L L V L I S I C W 5 45 E Q A K V F S H R 5 69 A F G SG I H K I 5 88 Y L K E V D V F V 5 90 K E V D V F V S M 5 95 F V S M G YH K K 5 113 F L K G G S D S D 5 136 R Y K C E V I E G 5 147 D D T V V VA L D 5 156 L Q G V V F P Y F 5 182 L D Q D A V I A S 5 195 Y D A W R GG L D 5 214 S V Q Y P I T K P 5 215 V Q Y P I T K P R 5 225 P C G G Q NT V P 5 245 K S R Y D V F C F 5 248 Y D V F C F T S N 5 259 G R F Y Y LI H P 5 314 V R Y P I S R P R 5 325 C S P T E A A V R 5 335 V G F P D KK H K 5 10 I S I C W A D H L 4 11 S I C W A D H L S 4 24 L D H D R A I HI 4 26 H D R A I H I Q A 4 42 V E A E Q A K V F 4 52 H R G G N V T L P 458 T L P C K F Y R D 4 107 G Y Q G R V F L K 4 112 V F L K G G S D S 4137 Y K C E V I E G L 4 164 F P R L G R Y N L 4 175 H E A Q Q A C L D 4180 A C L D Q D A V I 4 186 A V I A S F D Q L 4 197 A W R G G L D W C 4211 S D G S V Q Y P I 4 231 T V P G V R N Y G 4 238 Y G F W D K D K S 4256 N F N G R F Y Y L 4 262 Y Y L I H P T K L 4 273 D E A V Q A C L N 4281 N D G A Q I A K V 4 287 A K V G Q I F A A 4 310 A D G S V R Y P I 4324 R C S P T E A A V 4 328 T E A A V R F V G 4 331 A V R F V G F P D 4334 F V G F P D K K H 4 343 K L Y G V Y C F R 4 17 H L S D N Y T L D 329 A I H I Q A E N G 3 65 R D P T A F G S G 3 102 K K T Y G G Y Q G 3106 G G Y Q G R V F L 3 134 Y G R Y K C E V I 3 154 L D L Q G V V F P 3160 V F P Y F P R L G 3 163 Y F P R L G R Y N 3 165 P R L G R Y N L N 3169 R Y N L N F H E A 3 203 D W C N A G W L S 3 223 R E P C G G Q N T 3224 E P C G G Q N T V 3 228 G Q N T V P G V R 3 236 R N Y G F W D K D 3252 C F T S N F N G R 3 257 F N G R F Y Y L I 3 279 C L N D G A Q I A 3285 Q I A K V G Q I F 3 288 K V G Q I F A A W 3 302 D R C D A G W L A 3313 S V R Y P I S R P 3 319 S R P R R R C S P 3 329 E A A V R F V G F 3333 R F V G F P D K K 3 342 H K L Y G V Y C F 3 8 V L I S I C W A D 2 19S D N Y T L D H D 2 38 P H L L V E A E Q 2 44 A E Q A K V F S H 2 49 V FS H R G G N V 2 55 G N V T L P C K F 2 60 P C K F Y R D P T 2 63 F Y R DP T A F G 2 70 F G S G I H K I R 2 72 S G I H K I R I K 2 76 K I R I K WT K L 2 77 I R I K W T K L T 2 82 T K L T S D Y L K 2 86 S D Y L K E V DV 2 87 D Y L K E V D V F 2 94 V F V S M G Y H K 2 101 H K K T Y G G Y Q2 104 T Y G G Y Q G R V 2 121 D A S L V I T D L 2 124 L V I T D L T L E2 140 E V I E G L E D D 2 149 T V V V A L D L Q 2 152 V A L D L Q G V V2 170 Y N L N F H E A Q 2 191 F D Q L Y D A W R 2 208 G W L S D G S V Q2 212 D G S V Q Y P I T 2 217 Y P I T K P R E P 2 218 P I T K P R E P C2 229 Q N T V P G V R N 2 232 V P G V R N Y G F 2 234 G V R N Y G F W D2 251 F C F T S N F N G 2 269 K L T Y D E A V Q 2 276 V Q A C L N D G A2 278 A C L N D G A Q I 2 284 A Q I A K V G Q I 2 290 G Q I F A A W K I2 295 A W K I L G Y D R 2 296 W K I L G Y D R C 2 297 K I L G Y D R C D2 298 I L G Y D R C D A 2 301 Y D R C D A G W L 2 307 G W L A D G S V R2 316 Y P I S R P R R R 2 317 P I S R P R R R C 2 326 S P T E A A V R F2 330 A A V R F V G F P 2 336 G F P D K K H K L 2 341 K H K L Y G V Y C2 5 L L L V L I S I C 1 15 A D H L S D N Y T 1 16 D H L S D N Y T L 1 31H I Q A E N G P H 1 32 I Q A E N G P H L 1 37 G P H L L V E A E 1 39 H LL V E A E Q A 1 40 L L V E A E Q A K 1 47 A K V F S H R G G 1 48 K V F SH R G G N 1 66 D P T A F G S G I 1 111 R V F L K G G S D 1 114 L K G G SD S D A 1 128 D L T L E D Y G R 1 132 E D Y G R Y K C E 1 133 D Y G R YK C E V 1 143 E G L E D D T V V 1 151 V V A L D L Q G V 1 158 G V V F PY F P R 1 168 G R Y N L N F H E 1 171 N L N F H E A Q Q 1 177 A Q Q A CL D Q D 1 193 Q L Y D A W R G G 1 198 W R G G L D W C N 1 205 C N A G WL S D G 1 207 A G W L S D G S V 1 221 K P R E P C G G Q 1 227 G G Q N TV P G V 1 243 K D K S R Y D V F 1 244 D K S R Y D V F C 1 250 V F C F TS N F N 1 261 F Y Y L I H P T K 1 268 T K L T Y D E A V 1 275 A V Q A CL N D G 1 282 D G A Q I A K V G 1 289 V G Q I F A A W K 1 294 A A W K IL G Y D 1 304 C D A G W L A D G 1 306 A G W L A D G S V 1 315 R Y P I SR P R R 1 323 R R C S P T E A A 1 344 L Y G V Y C F R A 1 346 G V Y C FR A Y N 1 151P3D4 v.2: HLA Peptide Scoring Results A1 9-mers SYFPEITHI188 R K E K A E I H Y 29 123 N T N P S R R P Y 26 367 P A D L A G S G Y26 106 S F C R N K L K Y 25 59 F V G S Y K L A Y 23 302 S T Y D S L S PY 23 169 A P H E V G W K Y 21 220 Y T E S P G G G S 20 83 R K D K V L LG R 18 97 S C E G I N I S G 18 157 A S E A Y K K V C 17 212 N M K K K ID K Y 17 296 S C P T S S S T Y 17 55 G H V Q F V G S Y 16 69 N D G E H WT V Y 16 323 P S G G G G L K K 16 353 P K S E N N S W Y 16 153 P Q G H AS E A Y 15 361 Y V E N G R P A D 15 385 S L E E G L G G K 15 77 Y Q D EK Q R K D 14 354 K S E N N S W Y V 14 386 L E E G L G G K Q 14 400 K A EN G P H L L 14 7 K T F P L R A L H 13 21 I R D H S G Q K M 13 30 K Q D KK V D L L 13 51 A K D F G H V Q F 13 68 S N D G E H W T V 13 78 Q D E KQ R K D K 13 145 K A D G G S C C P 13 5 T T K T F P L R A 12 17 V V E SI R D H S 12 170 P H E V G W K Y Q 12 183 T L E E K R K E K 12 184 L E EK R K E K A 12 191 K A E I H Y R K N 12 208 Q A E K N M K K K 12 244 A TR A T R I G H 12 264 A H R P P A L S A 12 301 S S T Y D S L S P 12 1 M LE H T T K T F 11 4 H T T K T F P L R 11 34 K V D L L V P T K 11 40 P T KV T G I I T 11 216 K I D K Y T E S P 11 226 G G S P R G L G F 11 279 A SP A A W L P L 11 382 A I E S L E E G L 11 384 E S L E E G L G G 11 394 QK D K E R K A E 11 31 Q D K K V D L L V 10 70 D G E H W T V Y Q 10 74 WT V Y Q D E K Q 10 133 F Q V P S R I F W 10 142 R Q E K A D G G S 10 291W T R P S S C P T 10 295 S S C P T S S S T 10 303 T Y D S L S P Y G 10364 N G R P A D L A G 10 373 S G Y C G A L W K 10 396 D K E R K A E N G10 82 Q R K D K V L L G 9 112 L K Y L A F L H K 9 150 S C C P Q G H A S9 160 A Y K K V C L S G 9 180 V T A T L E E K R 9 182 A T L E E K R K E9 196 Y R K N K Q L M R 9 229 P R G L G F I F K 9 247 A T R I G H P G G9 300 S S S T Y D S L S 9 306 S L S P Y G P R N 9 67 Y S N D G E H W T 8222 E S P G G G S P R 8 310 Y G P R N P L P N 8 322 S P S G G G G L K 832 D K K V D L L V P 7 43 V T G I I T Q G A 7 47 I T Q G A K D F G 7 96V S C E G I N I S 7 105 G S F C R N K L K 7 127 S R R P Y H F Q V 7 199N K Q L M R L Q K 7 221 T E S P G G G S P 7 236 F K T I A P L A A 7 237K T I A P L A A T 7 250 I G H P G G R T P 7 256 R T P R A G S S A 7 272A R A P V P A A S 7 278 A A S P A A W L P 7 288 R T P W T R P S S 7 309P Y G P R N P L P 7 321 H S P S G G G G L 7 324 S G G G G L K K P 7 338G Q K H N V L A R 7 346 R G K P Q R K P K 7 372 G S G Y C G A L W 7 8 TF P L R A L H I 6 10 P L R A L H I V V 6 41 T K V T G I I T Q 6 54 F G HV Q F V G S 6 95 V V S C E G I N I 6 109 R N K L K Y L A F 6 166 L S G AP H E V G 6 167 S G A P H E V G W 6 178 Q A V T A T L E E 6 227 G S P RG L G F I 6 262 S S A H R P P A L 6 281 P A A W L P L R T 6 283 A W L PL R T P W 6 298 P T S S S T Y D S 6 307 L S P Y G P R N P 6 333 A R H CQ G Q K H 6 358 N S W Y V E N G R 6 380 W K A I E S L E E 6 13 A L H I VV E S I 5 23 D H S G Q K M K Q 5 35 V D L L V P T K V 5 37 L L V P T K VT G 5 45 G I I T Q G A K D 5 57 V Q F V G S Y K L 5 104 S G S F C R N KL 5 126 P S R R P Y H F Q 5 149 G S C C P Q G H A 5 204 R L Q K Q A E KN 5 223 S P G G G S P R G 5 261 G S S A H R P P A 5 263 S A H R P P A LS 5 274 A P V P A A S P A 5 294 P S S C P T S S S 5 305 D S L S P Y G PR 5 308 S P Y G P R N P L 5 320 R H S P S G G G G 5 329 L K K P A R H CQ 5 388 E G L G G K Q K D 5 15 H I V V E S I R D 4 19 E S I R D H S G Q4 24 H S G Q K M K Q D 4 27 Q K M K Q D K K V 4 61 G S Y K L A Y S N 487 V L L G R K A V V 4 102 N I S G S F C R N 4 103 I S G S F C R N K 4128 R R P Y H F Q V P 4 131 Y H F Q V P S R I 4 135 V P S R I F W R Q 4136 P S R I F W R Q E 4 177 Y Q A V T A T L E 4 211 K N M K K K I D K 4225 G G G S P R G L G 4 228 S P R G L G F I F 4 231 G L G F I F K T I 4233 G F I F K T I A P 4 238 T I A P L A A T R 4 251 G H P G G R T P R 4255 G R T P R A G S S 4 265 H R P P A L S A R 4 270 L S A R A P V P A 4271 S A R A P V P A A 4 280 S P A A W L P L R 4 287 L R T P W T R P S 4299 T S S S T Y D S L 4 312 P R N P L P N P R 4 314 N P L P N P R H S 4316 L P N P R H S P S 4 343 V L A R G K P Q R 4 345 A R G K P Q R K P 4350 Q R K P K S E N N 4 377 G A L W K A I E S 4 390 L G G K Q K D K E 422 R D H S G Q K M K 3 36 D L L V P T K V T 3 39 V P T K V T G I I 3 49Q G A K D F G H V 3 53 D F G H V Q F V G 3 56 H V Q F V G S Y K 3 58 Q FV G S Y K L A 3 63 Y K L A Y S N D G 3 85 D K V L L G R K A 3 86 K V L LG R K A V 3 90 G R K A V V V S C 3 91 R K A V V V S C E 3 111 K L K Y LA F L H 3 114 Y L A F L H K R M 3 130 P Y H F Q V P S R 3 137 S R I F WR Q E K 3 144 E K A D G G S C C 3 159 E A Y K K V C L S 3 164 V C L S GA P H E 3 173 V G W K Y Q A V T 3 192 A E I H Y R K N K 3 207 K Q A E KN M K K 3 209 A E K N M K K K I 3 230 R G L G F I F K T 3 269 A L S A RA P V P 3 315 P L P N P R H S P 3 335 H C Q G Q K H N V 3 337 Q G Q K HN V L A 3 341 H N V L A R G K P 3 355 S E N N S W Y V E 3 359 S W Y V EN G R P 3 363 E N G R P A D L A 3 368 A D L A G S G Y C 3 369 D L A G SG Y C G 3 371 A G S G Y C G A L 3 374 G Y C G A L W K A 3 387 E E G L GG K Q K 3 14 L H I V V E S I R 2 20 S I R D H S G Q K 2 25 S G Q K M K QD K 2 26 G Q K M K Q D K K 2 46 I I T Q G A K D F 2 50 G A K D F G H V Q2 52 K D F G H V Q F V 2 62 S Y K L A Y S N D 2 64 K L A Y S N D G E 266 A Y S N D G E H W 2 72 E H W T V Y Q D E 2 79 D E K Q R K D K V 2 81K Q R K D K V L L 2 88 L L G R K A V V V 2 89 L G R K A V V V S 2 92 K AV V V S C E G 2 101 I N I S G S F C R 2 108 C R N K L K Y L A 2 113 K YL A F L H K R 2 116 A F L H K R M N T 2 117 F L H K R M N T N 2 138 R IF W R Q E K A 2 139 I F W R Q E K A D 2 146 A D G G S C C P Q 2 151 C CP Q G H A S E 2 155 G H A S E A Y K K 2 156 H A S E A Y K K V 2 158 S EA Y K K V C L 2 161 Y K K V C L S G A 2 165 C L S G A P H E V 2 174 G WK Y Q A V T A 2 176 K Y Q A V T A T L 2 193 E I H Y R K N K Q 2 195 H YR K N K Q L M 2 197 R K N K Q L M R L 2 198 K N K Q L M R L Q 2 200 K QL M R L Q K Q 2 202 L M R L Q K Q A E 2 235 I F K T I A P L A 2 241 P LA A T R A T R 2 249 R I G H P G G R T 2 254 G G R T P R A G S 2 257 T PR A G S S A H 2 282 A A W L P L R T P 2 286 P L R T P W T R P 2 304 Y DS L S P Y G P 2 313 R N P L P N P R H 2 328 G L K K P A R H C 2 334 R HC Q G Q K H N 2 339 Q K H N V L A R G 2 347 G K P Q R K P K S 2 357 N NS W Y V E N G 2 362 V E N G R P A D L 2 370 L A G S G Y C G A 2 375 Y CG A L W K A I 2 378 A L W K A I E S L 2 379 L W K A I E S L E 2 383 I ES L E E G L G 2 389 G L G G K Q K D K 2 393 K Q K D K E R K A 2 6 T K TF P L R A L 1 9 F P L R A L H I V 1 11 L R A L H I V V E 1 12 R A L H IV V E S 1 18 V E S I R D H S G 1 28 K M K Q D K K V D 1 38 L V P T K V TG I 1 42 K V T G I I T Q G 1 60 V G S Y K L A Y S 1 71 G E H W T V Y Q D1 73 H W T V Y Q D E K 1 76 V Y Q D E K Q R K 1 80 E K Q R K D K V L 193 A V V V S C E G I 1 94 V V V S C E G I N 1 100 G I N I S G S F C 1107 F C R N K L K Y L 1 110 N K L K Y L A F L 1 115 L A F L H K R M N 1118 L H K R M N T N P 1 120 K R M N T N P S R 1 122 M N T N P S R R P 1124 T N P S R R P Y H 1 132 H F Q V P S R I F 1 140 F W R Q E K A D G 1143 Q E K A D G G S C 1 152 C P Q G H A S E A 1 163 K V C L S G A P H 1168 G A P H E V G W K 1 171 H E V G W K Y Q A 1 175 W K Y Q A V T A T 1179 A V T A T L E E K 1 194 I H Y R K N K Q L 1 201 Q L M R L Q K Q A 1206 Q K Q A E K N M K 1 224 P G G G S P R G L 1 234 F I F K T I A P L 1240 A P L A A T R A T 1 243 A A T R A T R I G 1 246 R A T R I G H P G 1248 T R I G H P G G R 1 252 H P G G R T P R A 1 258 P R A G S S A H R 1260 A G S S A H R P P 1 268 P A L S A R A P V 1 273 R A P V P A A S P 1276 V P A A S P A A W 1 277 P A A S P A A W L 1 284 W L P L R T P W T 1290 P W T R P S S C P 1 311 G P R N P L P N P 1 319 P R H S P S G G G 1325 G G G G L K K P A 1 336 C Q G Q K H N V L 1 342 N V L A R G K P Q 1344 L A R G K P Q R K 1 349 P Q R K P K S E N 1 352 K P K S E N N S W 1360 W Y V E N G R P A 1 398 E R K A E N G P H 1 399 R K A E N G P H L 1

[0823] TABLE XXIII SEQ. Pos 1 2 3 4 5 6 7 8 9 score ID NO. 151P3D4 v.1:HLA Peptide Scoring Results A*0201 9-mers SYFPEITHI 4 L L L L V L I S I28 88 Y L K E V D V F V 25 123 S L V I T D L T L 25 144 G L E D D T V VV 25 84 L T S D Y L K E V 23 76 K I R I K W T K L 22 151 V V A L D L Q GV 22 3 S L L L L V L I S 20 51 S H R G G N V T L 20 159 V V F P Y F P RL 20 263 Y L I H P T K L T 20 5 L L L V L I S I C 19 41 L V E A E Q A KV 19 69 A F G S G I H K I 19 137 Y K C E V I E G L 19 152 V A L D L Q GV V 19 2 K S L L L L V L I 18 22 Y T L D H D R A I 18 186 A V I A S F DQ L 18 279 C L N D G A Q I A 18 281 N D G A Q I A K V 18 291 Q I F A A WK I L 18 32 I Q A E N G P H L 17 34 A E N G P H L L V 17 121 D A S L V IT D L 17 227 G G Q N T V P G V 17 284 A Q I A K V G Q I 17 308 W L A D GS V R Y 17 1 M K S L L L L V L 16 7 L V L I S I C W A 16 33 Q A E N G PH L L 16 39 H L L V E A E Q A 16 86 S D Y L K E V D V 16 106 G G Y Q G RV F L 16 113 F L K G G S D S D 16 116 G G S D S D A S L 16 181 C L D Q DA V I A 16 262 Y Y L I H P T K L 16 336 G F P D K K H K L 16 40 L L V EA E Q A K 15 125 V I T D L T L E D 15 141 V I E G L E D D T 15 155 D L QG V V F P Y 15 179 Q A C L D Q D A V 15 180 A C L D Q D A V I 15 207 A GW L S D G S V 15 209 W L S D G S V Q Y 15 264 L I H P T K L T Y 15 298 IL G Y D R C D A 15 306 A G W L A D G S V 15 324 R C S P T E A A V 15 339D K K H K L Y G V 15 8 V L I S I C W A D 14 10 I S I C W A D H L 14 16 DH L S D N Y T L 14 142 I E G L E D D T V 14 146 E D D T V V V A L 14 148D T V V V A L D L 14 153 A L D L Q G V V F 14 164 F P R L G R Y N L 14201 G L D W C N A G W 14 224 E P C G G Q N T V 14 256 N F N G R F Y Y L14 268 T K L T Y D E A V 14 270 L T Y D E A V Q A 14 278 A C L N D G A QI 14 293 F A A W K I L G Y 14 297 K I L G Y D R C D 14 327 P T E A A V RF V 14 343 K L Y G V Y C F R 14 36 N G P H L L V E A 13 81 W T K L T S DY L 13 83 K L T S D Y L K E 13 104 T Y G G Y Q G R V 13 145 L E D D T VV V A 13 189 A S F D Q L Y D A 13 193 Q L Y D A W R G G 13 194 L Y D A WR G G L 13 202 L D W C N A G W L 13 272 Y D E A V Q A C L 13 287 A K V GQ I F A A 13 6 L L V L I S I C W 12 9 L I S I C W A D H 12 23 T L D H DR A I H 12 58 T L P C K F Y R D 12 118 S D S D A S L V I 12 124 L V I TD L T L E 12 133 D Y G R Y K C E V 12 154 L D L Q G V V F P 12 166 R L GR Y N L N F 12 171 N L N F H E A Q Q 12 174 F H E A Q Q A C L 12 187 V IA S F D Q L Y 12 214 S V Q Y P I T K P 12 230 N T V P G V R N Y 12 290 GQ I F A A W K I 12 301 Y D R C D A G W L 12 309 L A D G S V R Y P 12 11S I C W A D H L S 11 17 H L S D N Y T L D 11 24 L D H D R A I H I 11 49V F S H R G G N V 11 73 G I H K I R I K W 11 103 K T Y G G Y Q G R 11117 G S D S D A S L V 11 120 S D A S L V I T D 11 130 T L E D Y G R Y K11 140 E V I E G L E D D 11 143 E G L E D D T V V 11 211 S D G S V Q Y PI 11 257 F N G R F Y Y L I 11 269 K L T Y D E A V Q 11 275 A V Q A C L ND G 11 286 I A K V G Q I F A 11 294 A A W K I L G Y D 11 310 A D G S V RY P I 11 330 A A V R F V G F P 11 28 R A I H I Q A E N 10 29 A I H I Q AE N G 10 78 R I K W T K L T S 10 79 I K W T K L T S D 10 90 K E V D V FV S M 10 95 F V S M G Y H K K 10 96 V S M G Y H K K T 10 97 S M G Y H KK T Y 10 122 A S L V I T D L T 10 126 I T D L T L E D Y 10 128 D L T L ED Y G R 10 129 L T L E D Y G R Y 10 134 Y G R Y K C E V I 10 197 A W R GG L D W C 10 242 D K D K S R Y D V 10 260 R F Y Y L I H P T 10 285 Q I AK V G Q I F 10 304 C D A G W L A D G 10 313 S V R Y P I S R P 10 44 A EQ A K V F S H 9 57 V T L P C K F Y R 9 71 G S G I H K I R I 9 72 S G I HK I R I K 9 77 I R I K W T K L T 9 119 D S D A S L V I T 9 276 V Q A C LN D G A 9 346 G V Y C F R A Y N 9 31 H I Q A E N G P H 8 50 F S H R G GN V T 8 66 D P T A F G S G I 8 74 I H K I R I K W T 8 111 R V F L K G GS D 8 114 L K G G S D S D A 8 149 T V V V A L D L Q 8 169 R Y N L N F HE A 8 182 L D Q D A V I A S 8 205 C N A G W L S D G 8 210 L S D G S V QY P 8 219 I T K P R E P C G 8 246 S R Y D V F C F T 8 283 G A Q I A K VG Q 8 288 K V G Q I F A A W 8 323 R R C S P T E A A 8 342 H K L Y G V YC F 8 13 C W A D H L S D N 7 15 A D H L S D N Y T 7 37 G P H L L V E A E7 48 K V F S H R G G N 7 54 G G N V T L P C K 7 61 C K F Y R D P T A 763 F Y R D P T A F G 7 68 T A F G S G I H K 7 107 G Y Q G R V F L K 7150 V V V A L D L Q G 7 172 L N F H E A Q Q A 7 178 Q Q A C L D Q D A 7183 D Q D A V I A S F 7 196 D A W R G G L D W 7 217 Y P I T K P R E P 7231 T V P G V R N Y G 7 249 D V F C F T S N F 7 265 I H P T K L T Y D 7271 T Y D E A V Q A C 7 344 L Y G V Y C F R A 7 12 I C W A D H L S D 618 L S D N Y T L D H 6 19 S D N Y T L D H D 6 27 D R A I H I Q A E 6 30I H I Q A E N G P 6 52 H R G G N V T L P 6 91 E V D V F V S M G 6 99 G YH K K T Y G G 6 131 L E D Y G R Y K C 6 167 L G R Y N L N F H 6 170 Y NL N F H E A Q 6 177 A Q Q A C L D Q D 6 188 I A S F D Q L Y D 6 200 G GL D W C N A G 6 204 W C N A G W L S D 6 206 N A G W L S D G S 6 223 R EP C G G Q N T 6 234 G V R N Y G F W D 6 236 R N Y G F W D K D 6 253 F TS N F N G R F 6 259 G R F Y Y L I H P 6 267 P T K L T Y D E A 6 317 P IS R P R R R C 6 322 R R R C S P T E A 6 329 E A A V R F V G F 6 334 F VG F P D K K H 6 14 W A D H L S D N Y 5 46 Q A K V F S H R G 5 64 Y R D PT A F G S 5 87 D Y L K E V D V F 5 89 L K E V D V F V S 5 108 Y Q G R VF L K G 5 109 Q G R V F L K G G 5 112 V F L K G G S D S 5 136 R Y K C EV I E G 5 158 G V V F P Y F P R 5 215 V Q Y P I T K P R 5 218 P I T K PR E P C 5 221 K P R E P C G G Q 5 238 Y G F W D K D K S 5 239 G F W D KD K S R 5 255 S N F N G R F Y Y 5 261 F Y Y L I H P T K 5 277 Q A C L ND G A Q 5 280 L N D G A Q I A K 5 299 L G Y D R C D A G 5 305 D A G W LA D G S 5 326 S P T E A A V R F 5 331 A V R F V G F P D 5 332 V R F V GF P D K 5 333 R F V G F P D K K 5 25 D H D R A I H I Q 4 26 H D R A I HI Q A 4 35 E N G P H L L V E 4 42 V E A E Q A K V F 4 55 G N V T L P C KF 4 67 P T A F G S G I H 4 75 H K I R I K W T K 4 93 D V F V S M G Y H 4135 G R Y K C E V I E 4 147 D D T V V V A L D 4 161 F P Y F P R L G R 4162 P Y F P R L G R Y 4 190 S F D Q L Y D A W 4 191 F D Q L Y D A W R 4195 Y D A W R G G L D 4 199 R G G L D W C N A 4 212 D G S V Q Y P I T 4213 G S V Q Y P I T K 4 226 C G G Q N T V P G 4 245 K S R Y D V F C F 4289 V G Q I F A A W K 4 292 I F A A W K I L G 4 296 W K I L G Y D R C 4300 G Y D R C D A G W 4 302 D R C D A G W L A 4 303 R C D A G W L A D 4312 G S V R Y P I S R 4 314 V R Y P I S R P R 4 316 Y P I S R P R R R 4318 I S R P R R R C S 4 319 S R P R R R C S P 4 320 R P R R R C S P T 421 N Y T L D H D R A 3 38 P H L L V E A E Q 3 53 R G G N V T L P C 3 56N V T L P C K F Y 3 59 L P C K F Y R D P 3 62 K F Y R D P T A F 3 80 K WT K L T S D Y 3 82 T K L T S D Y L K 3 127 T D L T L E D Y G 3 139 C E VI E G L E D 3 156 L Q G V V F P Y F 3 163 Y F P R L G R Y N 3 168 G R YN L N F H E 3 173 N F H E A Q Q A C 3 185 D A V I A S F D Q 3 198 W R GG L D W C N 3 208 G W L S D G S V Q 3 232 V P G V R N Y G F 3 235 V R NY G F W D K 3 247 R Y D V F C F T S 3 248 Y D V F C F T S N 3 266 H P TK L T Y D E 3 295 A W K I L G Y D R 3 307 G W L A D G S V R 3 335 V G FP D K K H K 3 341 K H K L Y G V Y C 3 20 D N Y T L D H D R 2 43 E A E QA K V F S 2 47 A K V F S H R G G 2 65 R D P T A F G S G 2 70 F G S G I HK I R 2 94 V F V S M G Y H K 2 98 M G Y H K K T Y G 2 100 Y H K K T Y GG Y 2 102 K K T Y G G Y Q G 2 110 G R V F L K G G S 2 115 K G G S D S DA S 2 157 Q G V V F P Y F P 2 165 P R L G R Y N L N 2 175 H E A Q Q A CL D 2 176 E A Q Q A C L D Q 2 184 Q D A V I A S F D 2 228 G Q N T V P GV R 2 229 Q N T V P G V R N 2 244 D K S R Y D V F C 2 251 F C F T S N FN G 2 274 E A V Q A C L N D 2 325 C S P T E A A V R 2 328 T E A A V R FV G 2 340 K K H K L Y G V Y 2 345 Y G V Y C F R A Y 2 92 V D V F V S M GY 1 105 Y G G Y Q G R V F 1 160 V F P Y F P R L G 1 216 Q Y P I T K P RE 1 220 T K P R E P C G G 1 240 F W D K D K S R Y 1 241 W D K D K S R YD 1 250 V F C F T S N F N 1 252 C F T S N F N G R 1 258 N G R F Y Y L IH 1 273 D E A V Q A C L N 1 315 R Y P I S R P R R 1 337 F P D K K H K LY 1 45 E Q A K V F S H R −1 132 E D Y G R Y K C E −1 203 D W C N A G W LS −1 225 P C G G Q N T V P −1 222 P R E P C G G Q N −2 237 N Y G F W D KD K −2 233 P G V R N Y G F W −3 338 P D K K H K L Y G −3 151P3D4 v.2:HLA Peptide Scoring Results A*0201 9-mers SYFPEITHI 378 A L W K A I E SL 29 87 V L L G R K A V V 27 13 A L H I V V E S I 26 234 F I F K T I A PL 26 88 L L G R K A V V V 25 165 C L S G A P H E V 25 382 A I E S L E EG L 21 38 L V P T K V T G I 20 385 S L E E G L G G K 20 86 K V L L G R KA V 19 110 N K L K Y L A F L 19 231 G L G F I F K T I 19 237 K T I A P LA A T 19 9 F P L R A L H I V 18 10 P L R A L H I V V 18 37 L L V P T K VT G 18 52 K D F G H V Q F V 18 36 D L L V P T K V T 17 57 V Q F V G S YK L 17 114 Y L A F L H K R M 17 156 H A S E A Y K K V 17 176 K Y Q A V TA T L 17 238 T I A P L A A T R 17 271 S A R A P V P A A 17 284 W L P L RT P W T 17 308 S P Y G P R N P L 17 400 K A E N G P H L L 17 30 K Q D KK V D L L 16 68 S N D G E H W T V 16 158 S E A Y K K V C L 16 242 L A AT R A T R I 16 262 S S A H R P P A L 16 277 P A A S P A A W L 16 306 S LS P Y G P R N 16 343 V L A R G K P Q R 16 362 V E N G R P A D L 16 371 AG S G Y C G A L 16 35 V D L L V P T K V 15 45 G I I T Q G A K D 15 93 AV V V S C E G I 15 107 F C R N K L K Y L 15 127 S R R P Y H F Q V 15 138R I F W R Q E K A 15 197 R K N K Q L M R L 15 201 Q L M R L Q K Q A 15227 G S P R G L G F I 15 230 R G L G F I F K T 15 268 P A L S A R A P V15 381 K A I E S L E E G 15 399 R K A E N G P H L 15 6 T K T F P L R A L14 12 R A L H I V V E S 14 29 M K Q D K K V D L 14 104 S G S F C R N K L14 117 F L H K R M N T N 14 212 N M K K K I D K Y 14 216 K I D K Y T E SP 14 282 A A W L P L R T P 14 369 D L A G S G Y C G 14 33 K K V D L L VP T 13 34 K V D L L V P T K 13 64 K L A Y S N D G E 13 81 K Q R K D K VL L 13 95 V V S C E G I N I 13 172 E V G W K Y Q A V 13 183 T L E E K RK E K 13 194 I H Y R K N K Q L 13 241 P L A A T R A T R 13 249 R I G H PG G R T 13 269 A L S A R A P V P 13 279 A S P A A W L P L 13 321 H S P SG G G G L 13 335 H C Q G Q K H N V 13 370 L A G S G Y C G A 13 374 G Y CG A L W K A 13 389 G L G G K Q K D K 13 1 M L E H T T K T F 12 16 I V VE S I R D H 12 27 Q K M K Q D K K V 12 43 V T G I I T Q G A 12 49 Q G AK D F G H V 12 182 A T L E E K R K E 12 204 R L Q K Q A E K N 12 264 A HR P P A L S A 12 299 T S S S T Y D S L 12 302 S T Y D S L S P Y 12 336 CQ G Q K H N V L 12 7 K T F P L R A L H 11 20 S I R D H S G Q K 11 67 Y SN D G E H W T 11 113 K Y L A F L H K R 11 131 Y H F Q V P S R I 11 179 AV T A T L E E K 11 202 L M R L Q K Q A E 11 240 A P L A A T R A T 11 315P L P N P R H S P 11 324 S G G G G L K K P 11 328 G L K K P A R H C 11375 Y C G A L W K A I 11 11 L R A L H I V V E 10 31 Q D K K V D L L V 1039 V P T K V T G I I 10 42 K V T G I I T Q G 10 46 I I T Q G A K D F 1079 D E K Q R K D K V 10 96 V S C E G I N I S 10 100 G I N I S G S F C 10102 N I S G S F C R N 10 111 K L K Y L A F L H 10 161 Y K K V C L S G A10 175 W K Y Q A V T A T 10 180 V T A T L E E K R 10 209 A E K N M K K KI 10 224 P G G G S P R G L 10 239 I A P L A A T R A 10 247 A T R I G H PG G 10 256 R T P R A G S S A 10 270 L S A R A P V P A 10 291 W T R P S SC P T 10 295 S S C P T S S S T 10 354 K S E N N S W Y V 10 377 G A L W KA I E S 10 3 E H T T K T F P L 9 5 T T K T F P L R A 9 8 T F P L R A L HI 9 65 L A Y S N D G E H 9 116 A F L H K R M N T 9 121 R M N T N P S R R9 145 K A D G G S C C P 9 167 S G A P H E V G W 9 168 G A P H E V G W K9 173 V G W K Y Q A V T 9 178 Q A V T A T L E E 9 186 E K R K E K A E I9 200 K Q L M R L Q K Q 9 252 H P G G R T P R A 9 263 S A H R P P A L S9 272 A R A P V P A A S 9 273 R A P V P A A S P 9 280 S P A A W L P L R9 281 P A A W L P L R T 9 344 L A R G K P Q R K 9 361 Y V E N G R P A D9 15 H I V V E S I R D 8 21 I R D H S G Q K M 8 41 T K V T G I I T Q 847 I T Q G A K D F G 8 55 G H V Q F V G S Y 8 59 F V G S Y K L A Y 8 89L G R K A V V V S 8 90 G R K A V V V S C 8 134 Q V P S R I F W R 8 152 CP Q G H A S E A 8 207 K Q A E K N M K K 8 232 L G F I F K T I A 8 250 IG H P G G R T P 8 274 A P V P A A S P A 8 278 A A S P A A W L P 8 286 PL R T P W T R P 8 365 G R P A D L A G S 8 393 K Q K D K E R K A 8 28 K MK Q D K K V D 7 50 G A K D F G H V Q 7 60 V G S Y K L A Y S 7 77 Y Q D EK Q R K D 7 80 E K Q R K D K V L 7 92 K A V V V S C E G 7 108 C R N K LK Y L A 7 115 L A F L H K R M N 7 123 N T N P S R R P Y 7 159 E A Y K KV C L S 7 163 K V C L S G A P H 7 171 H E V G W K Y Q A 7 174 G W K Y QA V T A 7 184 L E E K R K E K A 7 193 E I H Y R K N K Q 7 203 M R L Q KQ A E K 7 215 K K I D K Y T E S 7 220 Y T E S P G G G S 7 223 S P G G GS P R G 7 243 A A T R A T R I G 7 244 A T R A T R I G H 7 265 H R P P AL S A R 7 266 R P P A L S A R A 7 275 P V P A A S P A A 7 283 A W L P LR T P W 7 288 R T P W T R P S S 7 311 G P R N P L P N P 7 325 G G G G LK K P A 7 61 G S Y K L A Y S N 6 63 Y K L A Y S N D G 6 71 G E H W T V YQ D 6 82 Q R K D K V L L G 6 83 R K D K V L L G R 6 85 D K V L L G R K A6 91 R K A V V V S C E 6 101 I N I S G S F C R 6 149 G S C C P Q G H A 6150 S C C P Q G H A S 6 151 C C P Q G H A S E 6 155 G H A S E A Y K K 6164 V C L S G A P H E 6 169 A P H E V G W K Y 6 191 K A E I H Y R K N 6221 T E S P G G G S P 6 233 G F I F K T I A P 6 235 I F K T I A P L A 6236 F K T I A P L A A 6 245 T R A T R I G H P 6 261 G S S A H R P P A 6276 V P A A S P A A W 6 285 L P L R T P W T R 6 322 S P S G G G G L K 6327 G G L K K P A R H 6 337 Q G Q K H N V L A 6 338 G Q K H N V L A R 6339 Q K H N V L A R G 6 360 W Y V E N G R P A 6 366 R P A D L A G S G 6368 A D L A G S G Y C 6 373 S G Y C G A L W K 6 386 L E E G L G G K Q 6395 K D K E R K A E N 6 51 A K D F G H V Q F 5 58 Q F V G S Y K L A 5 74W T V Y Q D E K Q 5 84 K D K V L L G R K 5 94 V V V S C E G I N 5 97 S CE G I N I S G 5 98 C E G I N I S G S 5 106 S F C R N K L K Y 5 120 K R MN T N P S R 5 137 S R I F W R Q E K 5 189 K E K A E I H Y R 5 226 G G SP R G L G F 5 228 S P R G L G F I F 5 248 T R I G H P G G R 5 251 G H PG G R T P R 5 254 G G R T P R A G S 5 259 R A G S S A H R P 5 287 L R TP W T R P S 5 316 L P N P R H S P S 5 342 N V L A R G K P Q 5 345 A R GK P Q R K P 5 357 N N S W Y V E N G 5 380 W K A I E S L E E 5 388 E G LG G K Q K D 5 4 H T T K T F P L R 4 14 L H I V V E S I R 4 17 V V E S IR D H S 4 18 V E S I R D H S G 4 40 P T K V T G I I T 4 54 F G H V Q F VG S 4 75 T V Y Q D E K Q R 4 112 L K Y L A F L H K 4 129 R P Y H F Q V PS 4 141 W R Q E K A D G G 4 146 A D G G S C C P Q 4 160 A Y K K V C L SG 4 177 Y Q A V T A T L E 4 192 A E I H Y R K N K 4 195 H Y R K N K Q LM 4 205 L Q K Q A E K N M 4 208 Q A E K N M K K K 4 246 R A T R I G H PG 4 255 G R T P R A G S S 4 296 S C P T S S S T Y 4 298 P T S S S T Y DS 4 304 Y D S L S P Y G P 4 314 N P L P N P R H S 4 323 P S G G G G L KK 4 326 G G G L K K P A R 4 329 L K K P A R H C Q 4 331 K P A R H C Q GQ 4 333 A R H C Q G Q K H 4 340 K H N V L A R G K 4 347 G K P Q R K P KS 4 355 S E N N S W Y V E 4 364 N G R P A D L A G 4 376 C G A L W K A IE 4 390 L G G K Q K D K E 4 23 D H S G Q K M K Q 3 26 G Q K M K Q D K K3 32 D K K V D L L V P 3 44 T G I I T Q G A K 3 56 H V Q F V G S Y K 3103 I S G S F C R N K 3 119 H K R M N T N P S 3 130 P Y H F Q V P S R 3133 F Q V P S R I F W 3 139 I F W R Q E K A D 3 140 F W R Q E K A D G 3162 K K V C L S G A P 3 166 L S G A P H E V G 3 187 K R K E K A E I H 3196 Y R K N K Q L M R 3 211 K N M K K K I D K 3 214 K K K I D K Y T E 3219 K Y T E S P G G G 3 257 T P R A G S S A H 3 258 P R A G S S A H R 3289 T P W T R P S S C 3 292 T R P S S C P T S 3 300 S S S T Y D S L S 3301 S S T Y D S L S P 3 307 L S P Y G P R N P 3 310 Y G P R N P L P N 3320 R H S P S G G G G 3 348 K P Q R K P K S E 3 352 K P K S E N N S W 3359 S W Y V E N G R P 3 384 E S L E E G L G G 3 397 K E R K A E N G P 32 L E H T T K T F P 2 25 S G Q K M K Q D K 2 48 T Q G A K D F G H 2 66 AY S N D G E H W 2 69 N D G E H W T V Y 2 70 D G E H W T V Y Q 2 73 H W TV Y Q D E K 2 76 V Y Q D E K Q R K 2 109 R N K L K Y L A F 2 144 E K A DG G S C C 2 148 G G S C C P Q G H 2 154 Q G H A S E A Y K 2 181 T A T LE E K R K 2 190 E K A E I H Y R K 2 213 M K K K I D K Y T 2 218 D K Y TE S P G G 2 225 G G G S P R G L G 2 260 A G S S A H R P P 2 293 R P S SC P T S S 2 294 P S S C P T S S S 2 303 T Y D S L S P Y G 2 305 D S L SP Y G P R 2 312 P R N P L P N P R 2 313 R N P L P N P R H 2 341 H N V LA R G K P 2 350 Q R K P K S E N N 2 356 E N N S W Y V E N 2 358 N S W YV E N G R 2 363 E N G R P A D L A 2 367 P A D L A G S G Y 2 372 G S G YC G A L W 2 383 I E S L E E G L G 2 391 G G K Q K D K E R 2 22 R D H S GQ K M K 1 62 S Y K L A Y S N D 1 99 E G I N I S G S F 1 105 G S F C R NK L K 1 118 L H K R M N T N P 1 124 T N P S R R P Y H 1 125 N P S R R PY H F 1 132 H F Q V P S R I F 1 135 V P S R I F W R Q 1 143 Q E K A D GG S C 1 157 A S E A Y K K V C 1 198 K N K Q L M R L Q 1 199 N K Q L M RL Q K 1 206 Q K Q A E K N M K 1 222 E S P G G G S P R 1 318 N P R H S PS G G 1 330 K K P A R H C Q G 1 332 P A R H C Q G Q K 1 334 R H C Q G QK H N 1 351 R K P K S E N N S 1 379 L W K A I E S L E 1 392 G K Q K D KE R K 1 53 D F G H V Q F V G −1 126 P S R R P Y H F Q −1 128 R R P Y H FQ V P −1 188 R K E K A E I H Y −1 229 P R G L G F I F K −1 297 C P T S SS T Y D −1 319 P R H S P S G G G −1 353 P K S E N N S W Y −1 396 D K E RK A E N G −1 72 E H W T V Y Q D E −2 78 Q D E K Q R K D K −2 136 P S R IF W R Q E −2 153 P Q G H A S E A Y −2 210 E K N M K K K I D −2 253 P G GR T P R A G −2 387 E E G L G G K Q K −2 170 P H E V G W K Y Q −3 185 E EK R K E K A E −3 290 P W T R P S S C P −3 398 E R K A E N G P H −4

[0824] TABLE XXIV SEQ. Pos 1 2 3 4 5 6 7 8 9 score ID NO. 151P3D4: HLAPeptide Scoring Results A*0202 9-mers SYFPEITHI NO DATA

[0825] TABLE XXV SEQ. Pos 1 2 3 4 5 6 7 8 9 score ID NO. 151P3D4: HLAPeptide Scoring Results A*0203 9-mers SYFPEITHI NO DATA

[0826] TABLE XXVI SEQ. Pos 1 2 3 4 5 6 7 8 9 score ID NO. 151P3D4 v.1:HLA Peptide Scoring Results A3 9-mers SYFPEITHI 153 A L D L Q G V V F 29209 W L S D G S V Q Y 26 130 T L E D Y G R Y K 24 166 R L G R Y N L N F24 264 L I H P T K L T Y 24 308 W L A D G S V R Y 24 343 K L Y G V Y C FR 24 40 L L V E A E Q A K 22 95 F V S M G Y H K K 22 111 R V F L K G G SD 22 186 A V I A S F D Q L 21 75 H K I R I K W T K 20 78 R I K W T K L TS 20 269 K L T Y D E A V Q 20 331 A V R F V G F P D 20 123 S L V I T D LT L 19 144 G L E D D T V V V 19 155 D L Q G V V F P Y 19 261 F Y Y L I HP T K 19 285 Q I A K V G Q I F 19 23 T L D H D R A I H 18 39 H L L V E AE Q A 18 150 V V V A L D L Q G 18 234 G V R N Y G F W D 18 289 V G Q I FA A W K 18 307 G W L A D G S V R 18 346 G V Y C F R A Y N 18 3 S L L L LV L I S 17 56 N V T L P C K F Y 17 62 K F Y R D P T A F 17 76 K I R I KW T K L 17 88 Y L K E V D V F V 17 113 F L K G G S D S D 17 181 C L D QD A V I A 17 193 Q L Y D A W R G G 17 249 D V F C F T S N F 17 288 K V GQ I F A A W 17 313 S V R Y P I S R P 17 333 R F V G F P D K K 17 4 L L LL V L I S I 16 9 L I S I C W A D H 16 51 S H R G G N V T L 16 83 K L T SD Y L K E 16 140 E V I E G L E D D 16 171 N L N F H E A Q Q 16 279 C L ND G A Q I A 16 5 L L L V L I S I C 15 29 A I H I Q A E N G 15 31 H I Q AE N G P H 15 41 L V E A E Q A K V 15 48 K V F S H R G G N 15 68 T A F GS G I H K 15 72 S G I H K I R I K 15 93 D V F V S M G Y H 15 103 K T Y GG Y Q G R 15 128 D L T L E D Y G R 15 187 V I A S F D Q L Y 15 213 G S VQ Y P I T K 15 270 L T Y D E A V Q A 15 275 A V Q A C L N D G 15 278 A CL N D G A Q I 15 297 K I L G Y D R C D 15 320 R P R R R C S P T 15 7 L VL I S I C W A 14 8 V L I S I C W A D 14 91 E V D V F V S M G 14 107 G YQ G R V F L K 14 124 L V I T D L T L E 14 158 G V V F P Y F P R 14 231 TV P G V R N Y G 14 243 K D K S R Y D V F 14 325 C S P T E A A V R 14 334F V G F P D K K H 14 340 K K H K L Y G V Y 14 42 V E A E Q A K V F 13 94V F V S M G Y H K 13 159 V V F P Y F P R L 13 180 A C L D Q D A V I 13201 G L D W C N A G W 13 263 Y L I H P T K L T 13 280 L N D G A Q I A K13 284 A Q I A K V G Q I 13 298 I L G Y D R C D A 13 326 S P T E A A V RF 13 335 V G F P D K K H K 13 17 H L S D N Y T L D 12 44 A E Q A K V F SH 12 50 F S H R G G N V T 12 80 K W T K L T S D Y 12 82 T K L T S D Y LK 12 125 V I T D L T L E D 12 151 V V A L D L Q G V 12 161 F P Y F P R LG R 12 162 P Y F P R L G R Y 12 183 D Q D A V I A S F 12 208 G W L S D GS V Q 12 214 S V Q Y P I T K P 12 235 V R N Y G F W D K 12 291 Q I F A AW K I L 12 295 A W K I L G Y D R 12 303 R C D A G W L A D 12 317 P I S RP R R R C 12 332 V R F V G F P D K 12 341 K H K L Y G V Y C 12 6 L L V LI S I C W 11 58 T L P C K F Y R D 11 86 S D Y L K E V D V 11 90 K E V DV F V S M 11 97 S M G Y H K K T Y 11 102 K K T Y G G Y Q G 11 105 Y G GY Q G R V F 11 106 G G Y Q G R V F L 11 196 D A W R G G L D W 11 197 A WR G G L D W C 11 215 V Q Y P I T K P R 11 228 G Q N T V P G V R 11 230 NT V P G V R N Y 11 255 S N F N G R F Y Y 11 293 F A A W K I L G Y 11 314V R Y P I S R P R 11 318 I S R P R R R C S 11 324 R C S P T E A A V 11329 E A A V R F V G F 11 2 K S L L L L V L I 10 28 R A I H I Q A E N 1035 E N G P H L L V E 10 54 G G N V T L P C K 10 87 D Y L K E V D V F 10112 V F L K G G S D S 10 129 L T L E D Y G R Y 10 141 V I E G L E D D T10 149 T V V V A L D L Q 10 222 P R E P C G G Q N 10 236 R N Y G F W D KD 10 237 N Y G F W D K D K 10 245 K S R Y D V F C F 10 258 N G R F Y Y LI H 10 312 G S V R Y P I S R 10 315 R Y P I S R P R R 10 316 Y P I S R PR R R 10 321 P R R R C S P T E 10 11 S I C W A D H L S 9 12 I C W A D HL S D 9 45 E Q A K V F S H R 9 53 R G G N V T L P C 9 57 V T L P C K F YR 9 73 G I H K I R I K W 9 118 S D S D A S L V I 9 126 I T D L T L E D Y9 145 L E D D T V V V A 9 184 Q D A V I A S F D 9 191 F D Q L Y D A W R9 204 W C N A G W L S D 9 218 P I T K P R E P C 9 223 R E P C G G Q N T9 229 Q N T V P G V R N 9 240 F W D K D K S R Y 9 254 T S N F N G R F Y9 319 S R P R R R C S P 9 322 R R R C S P T E A 9 328 T E A A V R F V G9 1 M K S L L L L V L 8 10 I S I C W A D H L 8 18 L S D N Y T L D H 8 20D N Y T L D H D R 8 26 H D R A I H I Q A 8 34 A E N G P H L L V 8 66 D PT A F G S G I 8 67 P T A F G S G I H 8 92 V D V F V S M G Y 8 100 Y H KK T Y G G Y 8 132 E D Y G R Y K C E 8 134 Y G R Y K C E V I 8 135 G R YK C E V I E 8 143 E G L E D D T V V 8 152 V A L D L Q G V V 8 154 L D LQ G V V F P 8 177 A Q Q A C L D Q D 8 219 I T K P R E P C G 8 221 K P RE P C G G Q 8 224 E P C G G Q N T V 8 239 G F W D K D K S R 8 247 R Y DV F C F T S 8 260 R F Y Y L I H P T 8 282 D G A Q I A K V G 8 299 L G YD R C D A G 8 301 Y D R C D A G W L 8 342 H K L Y G V Y C F 8 32 I Q A EN G P H L 7 38 P H L L V E A E Q 7 63 F Y R D P T A F G 7 65 R D P T A FG S G 7 74 I H K I R I K W T 7 108 Y Q G R V F L K G 7 139 C E V I E G LE D 7 142 I E G L E D D T V 7 148 D T V V V A L D L 7 164 F P R L G R YN L 7 167 L G R Y N L N F H 7 195 Y D A W R G G L D 7 207 A G W L S D GS V 7 225 P C G G Q N T V P 7 244 D K S R Y D V F C 7 246 S R Y D V F CF T 7 306 A G W L A D G S V 7 330 A A V R F V G F P 7 337 F P D K K H KL Y 7 345 Y G V Y C F R A Y 7 14 W A D H L S D N Y 6 16 D H L S D N Y TL 6 24 L D H D R A I H I 6 33 Q A E N G P H L L 6 49 V F S H R G G N V 661 C K F Y R D P T A 6 64 Y R D P T A F G S 6 70 F G S G I H K I R 6 79I K W T K L T S D 6 98 M G Y H K K T Y G 6 116 G G S D S D A S L 6 117 GS D S D A S L V 6 119 D S D A S L V I T 6 120 S D A S L V I T D 6 146 ED D T V V V A L 6 163 Y F P R L G R Y N 6 165 P R L G R Y N L N 6 172 LN F H E A Q Q A 6 205 C N A G W L S D G 6 232 V P G V R N Y G F 6 253 FT S N F N G R F 6 272 Y D E A V Q A C L 6 287 A K V G Q I F A A 6 290 GQ I F A A W K I 6 296 W K I L G Y D R C 6 300 G Y D R C D A G W 6 304 CD A G W L A D G 6 13 C W A D H L S D N 5 30 I H I Q A E N G P 5 55 G N VT L P C K F 5 69 A F G S G I H K I 5 77 I R I K W T K L T 5 101 H K K TY G G Y Q 5 109 Q G R V F L K G G 5 114 L K G G S D S D A 5 122 A S L VI T D L T 5 136 R Y K C E V I E G 5 156 L Q G V V F P Y F 5 168 G R Y NL N F H E 5 169 R Y N L N F H E A 5 174 F H E A Q Q A C L 5 188 I A S FD Q L Y D 5 192 D Q L Y D A W R G 5 199 R G G L D W C N A 5 202 L D W CN A G W L 5 217 Y P I T K P R E P 5 262 Y Y L I H P T K L 5 277 Q A C LN D G A Q 5 281 N D G A Q I A K V 5 283 G A Q I A K V G Q 5 286 I A K VG Q I F A 5 292 I F A A W K I L G 5 310 A D G S V R Y P I 5 323 R R C SP T E A A 5 15 A D H L S D N Y T 4 22 Y T L D H D R A I 4 36 N G P H L LV E A 4 43 E A E Q A K V F S 4 85 T S D Y L K E V D 4 89 L K E V D V F VS 4 115 K G G S D S D A S 4 138 K C E V I E G L E 4 147 D D T V V V A LD 4 170 Y N L N F H E A Q 4 175 H E A Q Q A C L D 4 179 Q A C L D Q D AV 4 189 A S F D Q L Y D A 4 194 L Y D A W R G G L 4 200 G G L D W C N AG 4 203 D W C N A G W L S 4 220 T K P R E P C G G 4 226 C G G Q N T V PG 4 233 P G V R N Y G F W 4 252 C F T S N F N G R 4 256 N F N G R F Y YL 4 265 I H P T K L T Y D 4 273 D E A V Q A C L N 4 294 A A W K I L G YD 4 302 D R C D A G W L A 4 338 P D K K H K L Y G 4 25 D H D R A I H I Q3 27 D R A I H I Q A E 3 46 Q A K V F S H R G 3 47 A K V F S H R G G 352 H R G G N V T L P 3 104 T Y G G Y Q G R V 3 121 D A S L V I T D L 3131 L E D Y G R Y K C 3 133 D Y G R Y K C E V 3 157 Q G V V F P Y F P 3176 E A Q Q A C L D Q 3 178 Q Q A C L D Q D A 3 216 Q Y P I T K P R E 3241 W D K D K S R Y D 3 248 Y D V F C F T S N 3 257 F N G R F Y Y L I 3268 T K L T Y D E A V 3 274 E A V Q A C L N D 3 305 D A G W L A D G S 337 G P H L L V E A E 2 60 P C K F Y R D P T 2 81 W T K L T S D Y L 2 96V S M G Y H K K T 2 127 T D L T L E D Y G 2 137 Y K C E V I E G L 2 173N F H E A Q Q A C 2 182 L D Q D A V I A S 2 190 S F D Q L Y D A W 2 198W R G G L D W C N 2 210 L S D G S V Q Y P 2 211 S D G S V Q Y P I 2 267P T K L T Y D E A 2 271 T Y D E A V Q A C 2 309 L A D G S V R Y P 2 311D G S V R Y P I S 2 327 P T E A A V R F V 2 336 G F P D K K H K L 2 339D K K H K L Y G V 2 19 S D N Y T L D H D 1 21 N Y T L D H D R A 1 71 G SG I H K I R I 1 84 L T S D Y L K E V 1 99 G Y H K K T Y G G 1 110 G R VF L K G G S 1 160 V F P Y F P R L G 1 185 D A V I A S F D Q 1 227 G G QN T V P G V 1 242 D K D K S R Y D V 1 276 V Q A C L N D G A 1 151P3D4v.2: HLA Peptide Scoring Results A3 9-mers SYFPEITHI 34 K V D L L V P TK 28 20 S I R D H S G Q K 27 56 H V Q F V G S Y K 27 238 T I A P L A A TR 26 88 L L G R K A V V V 25 179 A V T A T L E E K 25 241 P L A A T R AT R 25 385 S L E E G L G G K 25 163 K V C L S G A P H 24 269 A L S A R AP V P 24 373 S G Y C G A L W K 24 87 V L L G R K A V V 23 183 T L E E KR K E K 23 343 V L A R G K P Q R 23 389 G L G G K Q K D K 23 37 L L V PT K V T G 21 75 T V Y Q D E K Q R 21 111 K L K Y L A F L H 21 59 F V G SY K L A Y 20 86 K V L L G R K A V 20 323 P S G G G G L K K 20 10 P L R AL H I V V 19 42 K V T G I I T Q G 19 46 I I T Q G A K D F 19 134 Q V P SR I F W R 19 322 S P S G G G G L K 19 342 N V L A R G K P Q 19 346 R G KP Q R K P K 19 387 E E G L G G K Q K 19 1 M L E H T T K T F 18 112 L K YL A F L H K 18 199 N K Q L M R L Q K 18 201 Q L M R L Q K Q A 18 13 A LH I V V E S I 17 16 I V V E S I R D H 17 22 R D H S G Q K M K 17 45 G II T Q G A K D 17 154 Q G H A S E A Y K 17 192 A E I H Y R K N K 17 204 RL Q K Q A E K N 17 207 K Q A E K N M K K 17 264 A H R P P A L S A 17 306S L S P Y G P R N 17 332 P A R H C Q G Q K 17 344 L A R G K P Q R K 1736 D L L V P T K V T 16 44 T G I I T Q G A K 16 51 A K D F G H V Q F 16117 F L H K R M N T N 16 203 M R L Q K Q A E K 16 249 R I G H P G G R T16 340 K H N V L A R G K 16 369 D L A G S G Y C G 16 84 K D K V L L G RK 15 100 G I N I S G S F C 15 109 R N K L K Y L A F 15 137 S R I F W R QE K 15 206 Q K Q A E K N M K 15 226 G G S P R G L G F 15 256 R T P R A GS S A 15 257 T P R A G S S A H 15 302 S T Y D S L S P Y 15 361 Y V E N GR P A D 15 378 A L W K A I E S L 15 7 K T F P L R A L H 14 64 K L A Y SN D G E 14 138 R I F W R Q E K A 14 155 G H A S E A Y K K 14 169 A P H EV G W K Y 14 211 K N M K K K I D K 14 222 E S P G G G S P R 14 231 G L GF I F K T I 14 250 I G H P G G R T P 14 284 W L P L R T P W T 14 285 L PL R T P W T R 14 286 P L R T P W T R P 14 296 S C P T S S S T Y 14 315 PL P N P R H S P 14 328 G L K K P A R H C 14 78 Q D E K Q R K D K 13 93 AV V V S C E G I 13 95 V V S C E G I N I 13 106 S F C R N K L K Y 13 165C L S G A P H E V 13 176 K Y Q A V T A T L 13 187 K R K E K A E I H 13194 I H Y R K N K Q L 13 216 K I D K Y T E S P 13 228 S P R G L G F I F13 229 P R G L G F I F K 13 244 A T R A T R I G H 13 272 A R A P V P A AS 13 275 P V P A A S P A A 13 367 P A D L A G S G Y 13 26 G Q K M K Q DK K 12 38 L V P T K V T G I 12 69 N D G E H W T V Y 12 83 R K D K V L LG R 12 103 I S G S F C R N K 12 105 G S F C R N K L K 12 121 R M N T N PS R R 12 129 R P Y H F Q V P S 12 168 G A P H E V G W K 12 172 E V G W KY Q A V 12 174 G W K Y Q A V T A 12 190 E K A E I H Y R K 12 208 Q A E KN M K K K 12 237 K T I A P L A A T 12 273 R A P V P A A S P 12 274 A P VP A A S P A 12 366 R P A D L A G S G 12 14 L H I V V E S I R 11 17 V V ES I R D H S 11 25 S G Q K M K Q D K 11 76 V Y Q D E K Q R K 11 89 L G RK A V V V S 11 94 V V V S C E G I N 11 99 E G I N I S G S F 11 101 I N IS G S F C R 11 113 K Y L A F L H K R 11 114 Y L A F L H K R M 11 143 Q EK A D G G S C 11 181 T A T L E E K R K 11 196 Y R K N K Q L M R 11 221 TE S P G G G S P 11 234 F I F K T I A P L 11 248 T R I G H P G G R 11 255G R T P R A G S S 11 265 H R P P A L S A R 11 320 R H S P S G G G G 11327 G G L K K P A R H 11 353 P K S E N N S W Y 11 382 A I E S L E E G L11 11 L R A L H I V V E 10 12 R A L H I V V E S 10 73 H W T V Y Q D E K10 81 K Q R K D K V L L 10 90 G R K A V V V S C 10 102 N I S G S F C R N10 120 K R M N T N P S R 10 123 N T N P S R R P Y 10 125 N P S R R P Y HF 10 127 S R R P Y H F Q V 10 144 E K A D G G S C C 10 160 A Y K K V C LS G 10 188 R K E K A E I H Y 10 189 K E K A E I H Y R 10 193 E I H Y R KN K Q 10 246 R A T R I G H P G 10 251 G H P G G R T P R 10 258 P R A G SS A H R 10 283 A W L P L R T P W 10 330 K K P A R H C Q G 10 333 A R H CQ G Q K H 10 348 K P Q R K P K S E 10 364 N G R P A D L A G 10 368 A D LA G S G Y C 10 392 G K Q K D K E R K 10 395 K D K E R K A E N 10 8 T F PL R A L H I 9 19 E S I R D H S G Q 9 50 G A K D F G H V Q 9 55 G H V Q FV G S Y 9 61 G S Y K L A Y S N 9 65 L A Y S N D G E H 9 91 R K A V V V SC E 9 157 A S E A Y K K V C 9 167 S G A P H E V G W 9 214 K K K I D K YT E 9 215 K K I D K Y T E S 9 247 A T R I G H P G G 9 266 R P P A L S AR A 9 270 L S A R A P V P A 9 278 A A S P A A W L P 9 295 S S C P T S SS T 9 313 R N P L P N P R H 9 338 G Q K H N V L A R 9 384 E S L E E G LG G 9 399 R K A E N G P H L 9 15 H I V V E S I R D 8 28 K M K Q D K K VD 8 32 D K K V D L L V P 8 33 K K V D L L V P T 8 80 E K Q R K D K V L 882 Q R K D K V L L G 8 116 A F L H K R M N T 8 128 R R P Y H F Q V P 8150 S C C P Q G H A S 8 152 C P Q G H A S E A 8 212 N M K K K I D K Y 8230 R G L G F I F K T 8 240 A P L A A T R A T 8 263 S A H R P P A L S 8276 V P A A S P A A W 8 277 P A A S P A A W L 8 279 A S P A A W L P L 8280 S P A A W L P L R 8 282 A A W L P L R T P 8 289 T P W T R P S S C 8293 R P S S C P T S S 8 308 S P Y G P R N P L 8 312 P R N P L P N P R 8316 L P N P R H S P S 8 362 V E N G R P A D L 8 398 E R K A E N G P H 831 Q D K K V D L L V 7 48 T Q G A K D F G H 7 66 A Y S N D G E H W 7 68S N D G E H W T V 7 124 T N P S R R P Y H 7 136 P S R I F W R Q E 7 145K A D G G S C C P 7 151 C C P Q G H A S E 7 153 P Q G H A S E A Y 7 158S E A Y K K V C L 7 164 V C L S G A P H E 7 173 V G W K Y Q A V T 7 200K Q L M R L Q K Q 7 239 I A P L A A T R A 7 242 L A A T R A T R I 7 254G G R T P R A G S 7 259 R A G S S A H R P 7 271 S A R A P V P A A 7 288R T P W T R P S S 7 305 D S L S P Y G P R 7 310 Y G P R N P L P N 7 318N P R H S P S G G 7 326 G G G L K K P A R 7 331 K P A R H C Q G Q 7 339Q K H N V L A R G 7 350 Q R K P K S E N N 7 371 A G S G Y C G A L 7 381K A I E S L E E G 7 396 D K E R K A E N G 7 400 K A E N G P H L L 7 29 MK Q D K K V D L 6 35 V D L L V P T K V 6 41 T K V T G I I T Q 6 62 S Y KL A Y S N D 6 126 P S R R P Y H F Q 6 130 P Y H F Q V P S R 6 139 I F WR Q E K A D 6 140 F W R Q E K A D G 6 166 L S G A P H E V G 6 175 W K YQ A V T A T 6 182 A T L E E K R K E 6 185 E E K R K E K A E 6 186 E K RK E K A E I 6 217 I D K Y T E S P G 6 219 K Y T E S P G G G 6 227 G S PR G L G F I 6 235 I F K T I A P L A 6 236 F K T I A P L A A 6 243 A A TR A T R I G 6 262 S S A H R P P A L 6 267 P P A L S A R A P 6 268 P A LS A R A P V 6 290 P W T R P S S C P 6 291 W T R P S S C P T 6 301 S S TY D S L S P 6 314 N P L P N P R H S 6 321 H S P S G G G G L 6 334 R H CQ G Q K H N 6 337 Q G Q K H N V L A 6 349 P Q R K P K S E N 6 352 K P KS E N N S W 6 355 S E N N S W Y V E 6 359 S W Y V E N G R P 6 363 E N GR P A D L A 6 372 G S G Y C G A L W 6 377 G A L W K A I E S 6 379 L W KA I E S L E 6 386 L E E G L G G K Q 6 388 E G L G G K Q K D 6 391 G G KQ K D K E R 6 393 K Q K D K E R K A 6 397 K E R K A E N G P 6 5 T T K TF P L R A 5 9 F P L R A L H I V 5 18 V E S I R D H S G 5 21 I R D H S GQ K M 5 52 K D F G H V Q F V 5 53 D F G H V Q F V G 5 97 S C E G I N I SG 5 107 F C R N K L K Y L 5 110 N K L K Y L A F L 5 118 L H K R M N T NP 5 131 Y H F Q V P S R I 5 141 W R Q E K A D G G 5 142 R Q E K A D G GS 5 146 A D G G S C C P Q 5 148 G G S C C P Q G H 5 159 E A Y K K V C LS 5 162 K K V C L S G A P 5 171 H E V G W K Y Q A 5 177 Y Q A V T A T LE 5 178 Q A V T A T L E E 5 180 V T A T L E E K R 5 197 R K N K Q L M RL 5 202 L M R L Q K Q A E 5 209 A E K N M K K K I 5 223 S P G G G S P RG 5 233 G F I F K T I A P 5 253 P G G R T P R A G 5 281 P A A W L P L RT 5 294 P S S C P T S S S 5 309 P Y G P R N P L P 5 317 P N P R H S P SG 5 324 S G G G G L K K P 5 329 L K K P A R H C Q 5 336 C Q G Q K H N VL 5 358 N S W Y V E N G R 5 365 G R P A D L A G S 5 376 C G A L W K A IE 5 380 W K A I E S L E E 5 4 H T T K T F P L R 4 24 H S G Q K M K Q D 430 K Q D K K V D L L 4 40 P T K V T G I I T 4 47 I T Q G A K D F G 4 49Q G A K D F G H V 4 54 F G H V Q F V G S 4 58 Q F V G S Y K L A 4 60 V GS Y K L A Y S 4 63 Y K L A Y S N D G 4 67 Y S N D G E H W T 4 70 D G E HW T V Y Q 4 85 D K V L L G R K A 4 92 K A V V V S C E G 4 98 C E G I N IS G S 4 132 H F Q V P S R I F 4 133 F Q V P S R I F W 4 161 Y K K V C LS G A 4 191 K A E I H Y R K N 4 198 K N K Q L M R L Q 4 218 D K Y T E SP G G 4 220 Y T E S P G G G S 4 245 T R A T R I G H P 4 252 H P G G R TP R A 4 292 T R P S S C P T S 4 300 S S S T Y D S L S 4 311 G P R N P LP N P 4 351 R K P K S E N N S 4 354 K S E N N S W Y V 4 356 E N N S W YV E N 4 360 W Y V E N G R P A 4 383 I E S L E E G L G 4 394 Q K D K E RK A E 4 23 D H S G Q K M K Q 3 71 G E H W T V Y Q D 3 79 D E K Q R K D KV 3 96 V S C E G I N I S 3 119 H K R M N T N P S 3 135 V P S R I F W R Q3 147 D G G S C C P Q G 3 195 H Y R K N K Q L M 3 224 P G G G S P R G L3 260 A G S S A H R P P 3 261 G S S A H R P P A 3 287 L R T P W T R P S3 307 L S P Y G P R N P 3 341 H N V L A R G K P 3 345 A R G K P Q R K P3 375 Y C G A L W K A I 3 27 Q K M K Q D K K V 2 39 V P T K V T G I I 257 V Q F V G S Y K L 2 77 Y Q D E K Q R K D 2 104 S G S F C R N K L 2115 L A F L H K R M N 2 170 P H E V G W K Y Q 2 184 L E E K R K E K A 2225 G G G S P R G L G 2 232 L G F I F K T I A 2 299 T S S S T Y D S L 2304 Y D S L S P Y G P 2 325 G G G G L K K P A 2 335 H C Q G Q K H N V 2347 G K P Q R K P K S 2 370 L A G S G Y C G A 2 374 G Y C G A L W K A 22 L E H T T K T F P 1 3 E H T T K T F P L 1 6 T K T F P L R A L 1 43 V TG I I T Q G A 1 72 E H W T V Y Q D E 1 122 M N T N P S R R P 1 149 G S CC P Q G H A 1 156 H A S E A Y K K V 1 205 L Q K Q A E K N M 1 210 E K NM K K K I D 1 213 M K K K I D K Y T 1 297 C P T S S S T Y D 1 319 P R HS P S G G G 1

[0827] TABLE XXVII SEQ. Pos 1 2 3 4 5 6 7 8 9 score ID NO. 151P3D4 v.1:HLA Peptide Scoring Results A26 9-mers SYFPEITHI 155 D L Q G V V F P Y30 249 D V F C F T S N F 30 159 V V F P Y F P R L 28 129 L T L E D Y G RY 27 230 N T V P G V R N Y 27 186 A V I A S F D Q L 26 126 I T D L T L ED Y 25 140 E V I E G L E D D 24 148 D T V V V A L D L 24 91 E V D V F VS M G 23 93 D V F V S M G Y H 23 183 D Q D A V I A S F 23 187 V I A S FD Q L Y 23 285 Q I A K V G Q I F 23 329 E A A V R F V G F 23 264 L I H PT K L T Y 22 308 W L A D G S V R Y 22 87 D Y L K E V D V F 21 146 E D DT V V V A L 21 153 A L D L Q G V V F 21 209 W L S D G S V Q Y 21 253 F TS N F N G R F 21 56 N V T L P C K F Y 20 76 K I R I K W T K L 20 256 N FN G R F Y Y L 20 291 Q I F A A W K I L 20 81 W T K L T S D Y L 19 162 PY F P R L G R Y 19 166 R L G R Y N L N F 19 103 K T Y G G Y Q G R 18 121D A S L V I T D L 18 336 G F P D K K H K L 18 62 K F Y R D P T A F 17100 Y H K K T Y G G Y 17 151 V V A L D L Q G V 17 288 K V G Q I F A A W17 293 F A A W K I L G Y 17 84 L T S D Y L K E V 16 123 S L V I T D L TL 16 124 L V I T D L T L E 16 243 K D K S R Y D V F 16 267 P T K L T Y DE A 16 313 S V R Y P I S R P 16 340 K K H K L Y G V Y 16 7 L V L I S I CW A 15 16 D H L S D N Y T L 15 58 T L P C K F Y R D 15 90 K E V D V F VS M 15 95 F V S M G Y H K K 15 128 D L T L E D Y G R 15 137 Y K C E V IE G L 15 156 L Q G V V F P Y F 15 214 S V Q Y P I T K P 15 345 Y G V Y CF R A Y 15 5 L L L V L I S I C 14 42 V E A E Q A K V F 14 45 E Q A K V FS H R 14 48 K V F S H R G G N 14 83 K L T S D Y L K E 14 111 R V F L K GG S D 14 149 T V V V A L D L Q 14 158 G V V F P Y F P R 14 190 S F D Q LY D A W 14 219 I T K P R E P C G 14 240 F W D K D K S R Y 14 245 K S R YD V F C F 14 275 A V Q A C L N D G 14 326 S P T E A A V R F 14 327 P T EA A V R F V 14 342 H K L Y G V Y C F 14 343 K L Y G V Y C F R 14 1 M K SL L L L V L 13 3 S L L L L V L I S 13 4 L L L L V L I S I 13 14 W A D HL S D N Y 13 17 H L S D N Y T L D 13 27 D R A I H I Q A E 13 32 I Q A EN G P H L 13 80 K W T K L T S D Y 13 119 D S D A S L V I T 13 125 V I TD L T L E D 13 141 V I E G L E D D T 13 231 T V P G V R N Y G 13 270 L TY D E A V Q A 13 337 F P D K K H K L Y 13 339 D K K H K L Y G V 13 8 V LI S I C W A D 12 22 Y T L D H D R A I 12 29 A I H I Q A E N G 12 35 E NG P H L L V E 12 40 L L V E A E Q A K 12 41 L V E A E Q A K V 12 55 G NV T L P C K F 12 57 V T L P C K F Y R 12 69 A F G S G I H K I 12 73 G IH K I R I K W 12 88 Y L K E V D V F V 12 92 V D V F V S M G Y 12 113 F LK G G S D S D 12 116 G G S D S D A S L 12 132 E D Y G R Y K C E 12 150 VV V A L D L Q G 12 212 D G S V Q Y P I T 12 252 C F T S N F N G R 12 255S N F N G R F Y Y 12 297 K I L G Y D R C D 12 9 L I S I C W A D H 11 10I S I C W A D H L 11 25 D H D R A I H I Q 11 51 S H R G G N V T L 11 67P T A F G S G I H 11 78 R I K W T K L T S 11 105 Y G G Y Q G R V F 11147 D D T V V V A L D 11 181 C L D Q D A V I A 11 201 G L D W C N A G W11 218 P I T K P R E P C 11 232 V P G V R N Y G F 11 260 R F Y Y L I H PT 11 311 D G S V R Y P I S 11 317 P I S R P R R R C 11 334 F V G F P D KK H 11 346 G V Y C F R A Y N 11 11 S I C W A D H L S 10 23 T L D H D R AI H 10 31 H I Q A E N G P H 10 97 S M G Y H K K T Y 10 106 G G Y Q G R VF L 10 144 G L E D D T V V V 10 171 N L N F H E A Q Q 10 173 N F H E A QQ A C 10 174 F H E A Q Q A C L 10 193 Q L Y D A W R G G 10 194 L Y D A WR G G L 10 234 G V R N Y G F W D 10 254 T S N F N G R F Y 10 263 Y L I HP T K L T 10 279 C L N D G A Q I A 10 331 A V R F V G F P D 10 39 H L LV E A E Q A 9 130 T L E D Y G R Y K 9 164 F P R L G R Y N L 9 210 L S DG S V Q Y P 9 239 G F W D K D K S R 9 242 D K D K S R Y D V 9 262 Y Y LI H P T K L 9 269 K L T Y D E A V Q 9 271 T Y D E A V Q A C 9 272 Y D EA V Q A C L 9 333 R F V G F P D K K 9 6 L L V L I S I C W 8 33 Q A E N GP H L L 8 36 N G P H L L V E A 8 43 E A E Q A K V F S 8 66 D P T A F G SG I 8 94 V F V S M G Y H K 8 112 V F L K G G S D S 8 143 E G L E D D T VV 8 163 Y F P R L G R Y N 8 189 A S F D Q L Y D A 8 202 L D W C N A G WL 8 205 C N A G W L S D G 8 224 E P C G G Q N T V 8 273 D E A V Q A C LN 8 274 E A V Q A C L N D 8 282 D G A Q I A K V G 8 284 A Q I A K V G QI 8 287 A K V G Q I F A A 8 298 I L G Y D R C D A 8 301 Y D R C D A G WL 8 304 C D A G W L A D G 8 305 D A G W L A D G S 8 309 L A D G S V R YP 8 13 C W A D H L S D N 7 20 D N Y T L D H D R 7 49 V F S H R G G N V 772 S G I H K I R I K 7 120 S D A S L V I T D 7 133 D Y G R Y K C E V 7145 L E D D T V V V A 7 160 V F P Y F P R L G 7 176 E A Q Q A C L D Q 7192 D Q L Y D A W R G 7 244 D K S R Y D V F C 7 259 G R F Y Y L I H P 7281 N D G A Q I A K V 7 292 I F A A W K I L G 7 296 W K I L G Y D R C 7302 D R C D A G W L A 7 332 V R F V G F P D K 7 2 K S L L L L V L I 6 37G P H L L V E A E 6 44 A E Q A K V F S H 6 52 H R G G N V T L P 6 65 R DP T A F G S G 6 68 T A F G S G I H K 6 79 I K W T K L T S D 6 107 G Y QG R V F L K 6 136 R Y K C E V I E G 6 154 L D L Q G V V F P 6 165 P R LG R Y N L N 6 182 L D Q D A V I A S 6 185 D A V I A S F D Q 6 196 D A WR G G L D W 6 197 A W R G G L D W C 6 203 D W C N A G W L S 6 227 G G QN T V P G V 6 250 V F C F T S N F N 6 265 I H P T K L T Y D 6 19 S D N YT L D H D 5 54 G G N V T L P C K 5 59 L P C K F Y R D P 5 74 I H K I R IK W T 5 108 Y Q G R V F L K G 5 109 Q G R V F L K G G 5 169 R Y N L N FH E A 5 177 A Q Q A C L D Q D 5 246 S R Y D V F C F T 5 248 Y D V F C FT S N 5 294 A A W K I L G Y D 5 335 V G F P D K K H K 5 28 R A I H I Q AE N 4 30 I H I Q A E N G P 4 64 Y R D P T A F G S 4 89 L K E V D V F V S4 114 L K G G S D S D A 4 167 L G R Y N L N F H 4 172 L N F H E A Q Q A4 217 Y P I T K P R E P 4 233 P G V R N Y G F W 4 235 V R N Y G F W D K4 251 F C F T S N F N G 4 257 F N G R F Y Y L I 4 258 N G R F Y Y L I H4 280 L N D G A Q I A K 4 315 R Y P I S R P R R 4 316 Y P I S R P R R R4 324 R C S P T E A A V 4 330 A A V R F V G F P 4 61 C K F Y R D P T A 377 I R I K W T K L T 3 96 V S M G Y H K K T 3 99 G Y H K K T Y G G 3 104T Y G G Y Q G R V 3 117 G S D S D A S L V 3 175 H E A Q Q A C L D 3 178Q Q A C L D Q D A 3 180 A C L D Q D A V I 3 198 W R G G L D W C N 3 216Q Y P I T K P R E 3 221 K P R E P C G G Q 3 222 P R E P C G G Q N 3 223R E P C G G Q N T 3 225 P C G G Q N T V P 3 236 R N Y G F W D K D 3 238Y G F W D K D K S 3 241 W D K D K S R Y D 3 276 V Q A C L N D G A 3 290G Q I F A A W K I 3 300 G Y D R C D A G W 3 24 L D H D R A I H I 2 34 AE N G P H L L V 2 38 P H L L V E A E Q 2 46 Q A K V F S H R G 2 47 A K VF S H R G G 2 63 F Y R D P T A F G 2 70 F G S G I H K I R 2 75 H K I R IK W T K 2 85 T S D Y L K E V D 2 86 S D Y L K E V D V 2 110 G R V F L KG G S 2 115 K G G S D S D A S 2 131 L E D Y G R Y K C 2 135 G R Y K C EV I E 2 152 V A L D L Q G V V 2 168 G R Y N L N F H E 2 184 Q D A V I AS F D 2 200 G G L D W C N A G 2 206 N A G W L S D G S 2 207 A G W L S DG S V 2 208 G W L S D G S V Q 2 215 V Q Y P I T K P R 2 220 T K P R E PC G G 2 226 C G G Q N T V P G 2 229 Q N T V P G V R N 2 266 H P T K L TY D E 2 278 A C L N D G A Q I 2 283 G A Q I A K V G Q 2 295 A W K I L GY D R 2 299 L G Y D R C D A G 2 303 R C D A G W L A D 2 314 V R Y P I SR P R 2 318 I S R P R R R C S 2 319 S R P R R R C S P 2 322 R R R C S PT E A 2 323 R R C S P T E A A 2 325 C S P T E A A V R 2 338 P D K K H KL Y G 2 341 K H K L Y G V Y C 2 12 I C W A D H L S D 1 15 A D H L S D NY T 1 18 L S D N Y T L D H 1 21 N Y T L D H D R A 1 26 H D R A I H I Q A1 60 P C K F Y R D P T 1 71 G S G I H K I R I 1 82 T K L T S D Y L K 198 M G Y H K K T Y G 1 101 H K K T Y G G Y Q 1 102 K K T Y G G Y Q G 1118 S D S D A S L V I 1 127 T D L T L E D Y G 1 134 Y G R Y K C E V I 1139 C E V I E G L E D 1 161 F P Y F P R L G R 1 170 Y N L N F H E A Q 1179 Q A C L D Q D A V 1 191 F D Q L Y D A W R 1 195 Y D A W R G G L D 1199 R G G L D W C N A 1 204 W C N A G W L S D 1 211 S D G S V Q Y P I 1213 G S V Q Y P I T K 1 247 R Y D V F C F T S 1 261 F Y Y L I H P T K 1268 T K L T Y D E A V 1 277 Q A C L N D G A Q 1 286 I A K V G Q I F A 1289 V G Q I F A A W K 1 306 A G W L A D G S V 1 307 G W L A D G S V R 1310 A D G S V R Y P I 1 312 G S V R Y P I S R 1 320 R P R R R C S P T 1321 P R R R C S P T E 1 328 T E A A V R F V G 1 344 L Y G V Y C F R A 1151P3D4 v.2: HLA Peptide Scoring Results A26 9-mers SYFPEITHI 302 S T YD S L S P Y 27 234 F I F K T I A P L 26 123 N T N P S R R P Y 23 172 E VG W K Y Q A V 23 59 F V G S Y K L A Y 22 378 A L W K A I E S L 22 46 I IT Q G A K D F 21 382 A I E S L E E G L 21 99 E G I N I S G S F 19 114 YL A F L H K R M 19 1 M L E H T T K T F 18 102 N I S G S F C R N 18 212 NM K K K I D K Y 18 237 K T I A P L A A T 18 369 D L A G S G Y C G 18 16I V V E S I R D H 17 34 K V D L L V P T K 17 38 L V P T K V T G I 17 42K V T G I I T Q G 17 106 S F C R N K L K Y 17 109 R N K L K Y L A F 17193 E I H Y R K N K Q 17 4 H T T K T F P L R 16 7 K T F P L R A L H 1655 G H V Q F V G S Y 16 132 H F Q V P S R I F 16 134 Q V P S R I F W R16 197 R K N K Q L M R L 16 3 E H T T K T F P L 15 30 K Q D K K V D L L15 45 G I I T Q G A K D 15 80 E K Q R K D K V L 15 179 A V T A T L E E K15 238 T I A P L A A T R 15 385 S L E E G L G G K 15 36 D L L V P T K VT 14 110 N K L K Y L A F L 14 299 T S S S T Y D S L 14 6 T K T F P L R AL 13 13 A L H I V V E S I 13 51 A K D F G H V Q F 13 58 Q F V G S Y K LA 13 107 F C R N K L K Y L 13 117 F L H K R M N T N 13 138 R I F W R Q EK A 13 169 A P H E V G W K Y 13 180 V T A T L E E K R 13 182 A T L E E KR K E 13 216 K I D K Y T E S P 13 226 G G S P R G L G F 13 228 S P R G LG F I F 13 256 R T P R A G S S A 13 275 P V P A A S P A A 13 288 R T P WT R P S S 13 291 W T R P S S C P T 13 296 S C P T S S S T Y 13 353 P K SE N N S W Y 13 356 E N N S W Y V E N 13 367 P A D L A G S G Y 13 399 R KA E N G P H L 13 5 T T K T F P L R A 12 17 V V E S I R D H S 12 20 S I RD H S G Q K 12 21 I R D H S G Q K M 12 43 V T G I I T Q G A 12 47 I T QG A K D F G 12 53 D F G H V Q F V G 12 69 N D G E H W T V Y 12 74 W T VY Q D E K Q 12 75 T V Y Q D E K Q R 12 93 A V V V S C E G I 12 100 G I NI S G S F C 12 159 E A Y K K V C L S 12 163 K V C L S G A P H 12 183 T LE E K R K E K 12 188 R K E K A E I H Y 12 220 Y T E S P G G G S 12 224 PG G G S P R G L 12 231 G L G F I F K T I 12 247 A T R I G H P G G 12 298P T S S S T Y D S 12 306 S L S P Y G P R N 12 361 Y V E N G R P A D 1215 H I V V E S I R D 11 23 D H S G Q K M K Q 11 29 M K Q D K K V D L 1132 D K K V D L L V P 11 37 L L V P T K V T G 11 40 P T K V T G I I T 1156 H V Q F V G S Y K 11 57 V Q F V G S Y K L 11 64 K L A Y S N D G E 1172 E H W T V Y Q D E 11 86 K V L L G R K A V 11 87 V L L G R K A V V 1194 V V V S C E G I N 11 95 V V S C E G I N I 11 125 N P S R R P Y H F 11153 P Q G H A S E A Y 11 158 S E A Y K K V C L 11 165 C L S G A P H E V11 204 R L Q K Q A E K N 11 205 L Q K Q A E K N M 11 244 A T R A T R I GH 11 249 R I G H P G G R T 11 262 S S A H R P P A L 11 277 P A A S P A AW L 11 305 D S L S P Y G P R 11 321 H S P S G G G G L 11 328 G L K K P AR H C 11 343 V L A R G K P Q R 11 362 V E N G R P A D L 11 371 A G S G YC G A L 11 389 G L G G K Q K D K 11 19 E S I R D H S G Q 10 81 K Q R K DK V L L 10 88 L L G R K A V V V 10 111 K L K Y L A F L H 10 190 E K A EI H Y R K 10 194 I H Y R K N K Q L 10 195 H Y R K N K Q L M 10 201 Q L MR L Q K Q A 10 222 E S P G G G S P R 10 233 G F I F K T I A P 10 241 P LA A T R A T R 10 284 W L P L R T P W T 10 308 S P Y G P R N P L 10 315 PL P N P R H S P 10 336 C Q G Q K H N V L 10 342 N V L A R G K P Q 10 381K A I E S L E E G 10 388 E G L G G K Q K D 10 10 P L R A L H I V V 9 52K D F G H V Q F V 9 79 D E K Q R K D K V 9 104 S G S F C R N K L 9 116 AF L H K R M N T 9 144 E K A D G G S C C 9 147 D G G S C C P Q G 9 176 KY Q A V T A T L 9 185 E E K R K E K A E 9 186 E K R K E K A E I 9 215 KK I D K Y T E S 9 265 H R P P A L S A R 9 269 A L S A R A P V P 9 279 AS P A A W L P L 9 286 P L R T P W T R P 9 384 E S L E E G L G G 9 8 T FP L R A L H I 8 85 D K V L L G R K A 8 139 I F W R Q E K A D 8 218 D K YT E S P G G 8 235 I F K T I A P L A 8 396 D K E R K A E N G 8 400 K A EN G P H L L 8 24 H S G Q K M K Q D 7 33 K K V D L L V P T 7 49 Q G A K DF G H V 7 54 F G H V Q F V G S 7 62 S Y K L A Y S N D 7 70 D G E H W T VY Q 7 82 Q R K D K V L L G 7 83 R K D K V L L G R 7 84 K D K V L L G R K7 90 G R K A V V V S C 7 130 P Y H F Q V P S R 7 156 H A S E A Y K K V 7161 Y K K V C L S G A 7 198 K N K Q L M R L Q 7 210 E K N M K K K I D 7230 R G L G F I F K T 7 324 S G G G G L K K P 7 365 G R P A D L A G S 7374 G Y C G A L W K A 7 387 E E G L G G K Q K 7 398 E R K A E N G P H 711 L R A L H I V V E 6 12 R A L H I V V E S 6 60 V G S Y K L A Y S 6 89L G R K A V V V S 6 91 R K A V V V S C E 6 96 V S C E G I N I S 6 98 C EG I N I S G S 6 128 R R P Y H F Q V P 6 175 W K Y Q A V T A T 6 200 K QL M R L Q K Q 6 207 K Q A E K N M K K 6 208 Q A E K N M K K K 6 245 T RA T R I G H P 6 258 P R A G S S A H R 6 271 S A R A P V P A A 6 280 S PA A W L P L R 6 311 G P R N P L P N P 6 338 G Q K H N V L A R 6 339 Q KH N V L A R G 6 363 E N G R P A D L A 6 370 L A G S G Y C G A 6 71 G E HW T V Y Q D 5 77 Y Q D E K Q R K D 5 112 L K Y L A F L H K 5 113 K Y L AF L H K R 5 131 Y H F Q V P S R I 5 135 V P S R I F W R Q 5 167 S G A PH E V G W 5 168 G A P H E V G W K 5 189 K E K A E I H Y R 5 191 K A E IH Y R K N 5 227 G S P R G L G F I 5 248 T R I G H P G G R 5 272 A R A PV P A A S 5 344 L A R G K P Q R K 5 350 Q R K P K S E N N 5 357 N N S WY V E N G 5 395 K D K E R K A E N 5 9 F P L R A L H I V 4 41 T K V T G II T Q 4 126 P S R R P Y H F Q 4 137 S R I F W R Q E K 4 141 W R Q E K AD G G 4 150 S C C P Q G H A S 4 151 C C P Q G H A S E 4 152 C P Q G H AS E A 4 187 K R K E K A E I H 4 203 M R L Q K Q A E K 4 219 K Y T E S PG G G 4 223 S P G G G S P R G 4 229 P R G L G F I F K 4 252 H P G G R TP R A 4 266 R P P A L S A R A 4 276 V P A A S P A A W 4 282 A A W L P LR T P 4 292 T R P S S C P T S 4 295 S S C P T S S S T 4 303 T Y D S L SP Y G 4 320 R H S P S G G G G 4 327 G G L K K P A R H 4 335 H C Q G Q KH N V 4 346 R G K P Q R K P K 4 347 G K P Q R K P K S 4 351 R K P K S EN N S 4 366 R P A D L A G S G 4 386 L E E G L G G K Q 4 391 G G K Q K DK E R 4 393 K Q K D K E R K A 4 14 L H I V V E S I R 3 26 G Q K M K Q DK K 3 27 Q K M K Q D K K V 3 44 T G I I T Q G A K 3 61 G S Y K L A Y S N3 68 S N D G E H W T V 3 76 V Y Q D E K Q R K 3 97 S C E G I N I S G 3101 I N I S G S F C R 3 115 L A F L H K R M N 3 124 T N P S R R P Y H 3127 S R R P Y H F Q V 3 133 F Q V P S R I F W 3 145 K A D G G S C C P 3146 A D G G S C C P Q 3 155 G H A S E A Y K K 3 160 A Y K K V C L S G 3164 V C L S G A P H E 3 171 H E V G W K Y Q A 3 174 G W K Y Q A V T A 3192 A E I H Y R K N K 3 196 Y R K N K Q L M R 3 202 L M R L Q K Q A E 3221 T E S P G G G S P 3 251 G H P G G R T P R 3 255 G R T P R A G S S 3259 R A G S S A H R P 3 264 A H R P P A L S A 3 267 P P A L S A R A P 3273 R A P V P A A S P 3 274 A P V P A A S P A 3 281 P A A W L P L R T 3283 A W L P L R T P W 3 309 P Y G P R N P L P 3 312 P R N P L P N P R 3313 R N P L P N P R H 3 314 N P L P N P R H S 3 316 L P N P R H S P S 3317 P N P R H S P S G 3 318 N P R H S P S G G 3 323 P S G G G G L K K 3325 G G G G L K K P A 3 326 G G G L K K P A R 3 329 L K K P A R H C Q 3331 K P A R H C Q G Q 3 333 A R H C Q G Q K H 3 349 P Q R K P K S E N 3352 K P K S E N N S W 3 364 N G R P A D L A G 3 390 L G G K Q K D K E 3394 Q K D K E R K A E 3 22 R D H S G Q K M K 2 25 S G Q K M K Q D K 2 28K M K Q D K K V D 2 31 Q D K K V D L L V 2 48 T Q G A K D F G H 2 50 G AK D F G H V Q 2 65 L A Y S N D G E H 2 78 Q D E K Q R K D K 2 103 I S GS F C R N K 2 105 G S F C R N K L K 2 108 C R N K L K Y L A 2 118 L H KR M N T N P 2 120 K R M N T N P S R 2 121 R M N T N P S R R 2 140 F W RQ E K A D G 2 142 R Q E K A D G G S 2 143 Q E K A D G G S C 2 148 G G SC C P Q G H 2 154 Q G H A S E A Y K 2 162 K K V C L S G A P 2 173 V G WK Y Q A V T 2 184 L E E K R K E K A 2 209 A E K N M K K K I 2 211 K N MK K K I D K 2 213 M K K K I D K Y T 2 217 I D K Y T E S P G 2 232 L G FI F K T I A 2 239 I A P L A A T R A 2 242 L A A T R A T R I 2 250 I G HP G G R T P 2 254 G G R T P R A G S 2 257 T P R A G S S A H 2 268 P A LS A R A P V 2 270 L S A R A P V P A 2 278 A A S P A A W L P 2 287 L R TP W T R P S 2 289 T P W T R P S S C 2 293 R P S S C P T S S 2 294 P S SC P T S S S 2 297 C P T S S S T Y D 2 304 Y D S L S P Y G P 2 307 L S PY G P R N P 2 319 P R H S P S G G G 2 322 S P S G G G G L K 2 330 K K PA R H C Q G 2 334 R H C Q G Q K H N 2 337 Q G Q K H N V L A 2 340 K H NV L A R G K 2 345 A R G K P Q R K P 2 348 K P Q R K P K S E 2 360 W Y VE N G R P A 2 375 Y C G A L W K A I 2 376 C G A L W K A I E 2 377 G A LW K A I E S 2 379 L W K A I E S L E 2 380 W K A I E S L E E 2 392 G K QK D K E R K 2 397 K E R K A E N G P 2 18 V E S I R D H S G 1 35 V D L LV P T K V 1 39 V P T K V T G I I 1 66 A Y S N D G E H W 1 67 Y S N D G EH W T 1 73 H W T V Y Q D E K 1 92 K A V V V S C E G 1 122 M N T N P S RR P 1 129 R P Y H F Q V P S 1 136 P S R I F W R Q E 1 149 G S C C P Q GH A 1 177 Y Q A V T A T L E 1 178 Q A V T A T L E E 1 181 T A T L E E KR K 1 199 N K Q L M R L Q K 1 206 Q K Q A E K N M K 1 214 K K K I D K YT E 1 225 G G G S P R G L G 1 236 F K T I A P L A A 1 240 A P L A A T RA T 1 253 P G G R T P R A G 1 260 A G S S A H R P P 1 261 G S S A H R PP A 1 263 S A H R P P A L S 1 290 P W T R P S S C P 1 300 S S S T Y D SL S 1 301 S S T Y D S L S P 1 310 Y G P R N P L P N 1 332 P A R H C Q GQ K 1 341 H N V L A R G K P 1 355 S E N N S W Y V E 1 358 N S W Y V E NG R 1 359 S W Y V E N G R P 1 372 G S G Y C G A L W 1

[0828] TABLE XXVIII SEQ. Pos 1 2 3 4 5 6 7 8 9 score ID NO. 151P3D4 v.1:HLA Peptide Scoring Results B*0702 9-mers SYFPEITHI 164 F P R L G R Y NL 23 320 R P R R R C S P T 20 224 E P C G G Q N T V 19 66 D P T A F G SG I 18 326 S P T E A A V R F 18 232 V P G V R N Y G F 17 51 S H R G G NV T L 16 146 E D D T V V V A L 16 161 F P Y F P R L G R 16 221 K P R E PC G G Q 16 1 M K S L L L L V L 15 34 A E N G P H L L V 15 32 I Q A E N GP H L 14 76 K I R I K W T K L 14 106 G G Y Q G R V F L 14 186 A V I A SF D Q L 14 116 G G S D S D A S L 13 121 D A S L V I T D L 13 153 A L D LQ G V V F 13 159 V V F P Y F P R L 13 194 L Y D A W R G G L 13 256 N F NG R F Y Y L 13 37 G P H L L V E A E 12 123 S L V I T D L T L 12 148 D TV V V A L D L 12 174 F H E A Q Q A C L 12 266 H P T K L T Y D E 12 272 YD E A V Q A C L 12 301 Y D R C D A G W L 12 323 R R C S P T E A A 12 324R C S P T E A A V 12 337 F P D K K H K L Y 12 10 I S I C W A D H L 11 59L P C K F Y R D P 11 118 S D S D A S L V I 11 145 L E D D T V V V A 11262 Y Y L I H P T K L 11 287 A K V G Q I F A A 11 291 Q I F A A W K I L11 310 A D G S V R Y P I 11 329 E A A V R F V G F 11 16 D H L S D N Y TL 10 33 Q A E N G P H L L 10 81 W T K L T S D Y L 10 90 K E V D V F V SM 10 119 D S D A S L V I T 10 137 Y K C E V I E G L 10 144 G L E D D T VV V 10 166 R L G R Y N L N F 10 180 A C L D Q D A V I 10 202 L D W C N AG W L 10 217 Y P I T K P R E P 10 245 K S R Y D V F C F 10 263 Y L I H PT K L T 10 278 A C L N D G A Q I 10 284 A Q I A K V G Q I 10 316 Y P I SR P R R R 10 322 R R R C S P T E A 10 336 G F P D K K H K L 10 2 K S L LL L V L I 9 26 H D R A I H I Q A 9 49 V F S H R G G N V 9 62 K F Y R D PT A F 9 69 A F G S G I H K I 9 77 I R I K W T K L T 9 87 D Y L K E V D VF 9 88 Y L K E V D V F V 9 96 V S M G Y H K K T 9 104 T Y G G Y Q G R V9 105 Y G G Y Q G R V F 9 114 L K G G S D S D A 9 122 A S L V I T D L T9 134 Y G R Y K C E V I 9 143 E G L E D D T V V 9 156 L Q G V V F P Y F9 181 C L D Q D A V I A 9 183 D Q D A V I A S F 9 212 D G S V Q Y P I T9 242 D K D K S R Y D V 9 281 N D G A Q I A K V 9 285 Q I A K V G Q I F9 298 I L G Y D R C D A 9 327 P T E A A V R F V 9 15 A D H L S D N Y T 836 N G P H L L V E A 8 41 L V E A E Q A K V 8 42 V E A E Q A K V F 8 50F S H R G G N V T 8 60 P C K F Y R D P T 8 63 F Y R D P T A F G 8 84 L TS D Y L K E V 8 86 S D Y L K E V D V 8 141 V I E G L E D D T 8 142 I E GL E D D T V 8 169 R Y N L N F H E A 8 189 A S F D Q L Y D A 8 199 R G GL D W C N A 8 207 A G W L S D G S V 8 211 S D G S V Q Y P I 8 223 R E PC G G Q N T 8 227 G G Q N T V P G V 8 243 K D K S R Y D V F 8 246 S R YD V F C F T 8 253 F T S N F N G R F 8 260 R F Y Y L I H P T 8 270 L T YD E A V Q A 8 286 I A K V G Q I F A 8 306 A G W L A D G S V 8 22 Y T L DH D R A I 7 61 C K F Y R D P T A 7 71 G S G I H K I R I 7 74 I H K I R IK W T 7 117 G S D S D A S L V 7 133 D Y G R Y K C E V 7 151 V V A L D LQ G V 7 152 V A L D L Q G V V 7 178 Q Q A C L D Q D A 7 179 Q A C L D QD A V 7 249 D V F C F T S N F 7 257 F N G R F Y Y L I 7 268 T K L T Y DE A V 7 276 V Q A C L N D G A 7 302 D R C D A G W L A 7 342 H K L Y G VY C F 7 344 L Y G V Y C F R A 7 4 L L L L V L I S I 6 7 L V L I S I C WA 6 21 N Y T L D H D R A 6 24 L D H D R A I H I 6 35 E N G P H L L V E 639 H L L V E A E Q A 6 53 R G G N V T L P C 6 55 G N V T L P C K F 6 172L N F H E A Q Q A 6 197 A W R G G L D W C 6 218 P I T K P R E P C 6 229Q N T V P G V R N 6 267 P T K L T Y D E A 6 279 C L N D G A Q I A 6 290G Q I F A A W K I 6 303 R C D A G W L A D 6 317 P I S R P R R R C 6 331A V R F V G F P D 6 339 D K K H K L Y G V 6 52 H R G G N V T L P 5 188 IA S F D Q L Y D 5 225 P C G G Q N T V P 5 226 C G G Q N T V P G 5 244 DK S R Y D V F C 5 288 K V G Q I F A A W 5 313 S V R Y P I S R P 5 318 IS R P R R R C S 5 12 I C W A D H L S D 4 18 L S D N Y T L D H 4 43 E A EQ A K V F S 4 44 A E Q A K V F S H 4 45 E Q A K V F S H R 4 56 N V T L PC K F Y 4 70 F G S G I H K I R 4 108 Y Q G R V F L K G 4 154 L D L Q G VV F P 4 155 D L Q G V V F P Y 4 158 G V V F P Y F P R 4 209 W L S D G SV Q Y 4 210 L S D G S V Q Y P 4 214 S V Q Y P I T K P 4 258 N G R F Y YL I H 4 280 L N D G A Q I A K 4 304 C D A G W L A D G 4 309 L A D G S VR Y P 4 328 T E A A V R F V G 4 330 A A V R F V G F P 4 334 F V G F P DK K H 4 341 K H K L Y G V Y C 4 343 K L Y G V Y C F R 4 3 S L L L L V LI S 3 9 L I S I C W A D H 3 17 H L S D N Y T L D 3 23 T L D H D R A I H3 68 T A F G S G I H K 3 78 R I K W T K L T S 3 80 K W T K L T S D Y 383 K L T S D Y L K E 3 91 E V D V F V S M G 3 103 K T Y G G Y Q G R 3107 G Y Q G R V F L K 3 115 K G G S D S D A S 3 125 V I T D L T L E D 3132 E D Y G R Y K C E 3 135 G R Y K C E V I E 3 139 C E V I E G L E D 3150 V V V A L D L Q G 3 167 L G R Y N L N F H 3 176 E A Q Q A C L D Q 3177 A Q Q A C L D Q D 3 196 D A W R G G L D W 3 198 W R G G L D W C N 3204 W C N A G W L S D 3 205 C N A G W L S D G 3 215 V Q Y P I T K P R 3219 I T K P R E P C G 3 231 T V P G V R N Y G 3 234 G V R N Y G F W D 3236 R N Y G F W D K D 3 264 L I H P T K L T Y 3 269 K L T Y D E A V Q 3271 T Y D E A V Q A C 3 274 E A V Q A C L N D 3 275 A V Q A C L N D G 3292 I F A A W K I L G 3 293 F A A W K I L G Y 3 294 A A W K I L G Y D 3295 A W K I L G Y D R 3 297 K I L G Y D R C D 3 307 G W L A D G S V R 3308 W L A D G S V R Y 3 311 D G S V R Y P I S 3 315 R Y P I S R P R R 3321 P R R R C S P T E 3 333 R F V G F P D K K 3 338 P D K K H K L Y G 3340 K K H K L Y G V Y 3 27 D R A I H I Q A E 2 28 R A I H I Q A E N 2 29A I H I Q A E N G 2 31 H I Q A E N G P H 2 47 A K V F S H R G G 2 48 K VF S H R G G N 2 64 Y R D P T A F G S 2 65 R D P T A F G S G 2 73 G I H KI R I K W 2 79 I K W T K L T S D 2 85 T S D Y L K E V D 2 89 L K E V D VF V S 2 95 F V S M G Y H K K 2 99 G Y H K K T Y G G 2 102 K K T Y G G YQ G 2 109 Q G R V F L K G G 2 111 R V F L K G G S D 2 112 V F L K G G SD S 2 113 F L K G G S D S D 2 120 S D A S L V I T D 2 126 I T D L T L ED Y 2 131 L E D Y G R Y K C 2 136 R Y K C E V I E G 2 147 D D T V V V AL D 2 165 P R L G R Y N L N 2 182 L D Q D A V I A S 2 184 Q D A V I A SF D 2 190 S F D Q L Y D A W 2 195 Y D A W R G G L D 2 201 G L D W C N AG W 2 208 G W L S D G S V Q 2 222 P R E P C G G Q N 2 230 N T V P G V RN Y 2 240 F W D K D K S R Y 2 247 R Y D V F C F T S 2 248 Y D V F C F TS N 2 254 T S N F N G R F Y 2 265 I H P T K L T Y D 2 282 D G A Q I A KV G 2 283 G A Q I A K V G Q 2 300 G Y D R C D A G W 2 314 V R Y P I S RP R 2 325 C S P T E A A V R 2 332 V R F V G F P D K 2 345 Y G V Y C F RA Y 2 346 G V Y C F R A Y N 2 8 V L I S I C W A D 1 13 C W A D H L S D N1 14 W A D H L S D N Y 1 25 D H D R A I H I Q 1 30 I H I Q A E N G P 138 P H L L V E A E Q 1 40 L L V E A E Q A K 1 54 G G N V T L P C K 1 57V T L P C K F Y R 1 58 T L P C K F Y R D 1 67 P T A F G S G I H 1 94 V FV S M G Y H K 1 97 S M G Y H K K T Y 1 98 M G Y H K K T Y G 1 100 Y H KK T Y G G Y 1 101 H K K T Y G G Y Q 1 124 L V I T D L T L E 1 130 T L ED Y G R Y K 1 138 K C E V I E G L E 1 140 E V I E G L E D D 1 157 Q G VV F P Y F P 1 162 P Y F P R L G R Y 1 163 Y F P R L G R Y N 1 170 Y N LN F H E A Q 1 171 N L N F H E A Q Q 1 173 N F H E A Q Q A C 1 175 H E AQ Q A C L D 1 187 V I A S F D Q L Y 1 191 F D Q L Y D A W R 1 200 G G LD W C N A G 1 203 D W C N A G W L S 1 206 N A G W L S D G S 1 216 Q Y PI T K P R E 1 228 G Q N T V P G V R 1 233 P G V R N Y G F W 1 235 V R NY G F W D K 1 237 N Y G F W D K D K 1 250 V F C F T S N F N 1 252 C F TS N F N G R 1 255 S N F N G R F Y Y 1 261 F Y Y L I H P T K 1 273 D E AV Q A C L N 1 277 Q A C L N D G A Q 1 289 V G Q I F A A W K 1 299 L G YD R C D A G 1 305 D A G W L A D G S 1 319 S R P R R R C S P 1 335 V G FP D K K H K 1 151P3D4 v.2: HLA Peptide Scoring Results B*0702 9-mersSYFPEITHI 308 S P Y G P R N P L 27 228 S P R G L G F I F 21 240 A P L AA T R A T 21 252 H P G G R T P R A 21 274 A P V P A A S P A 20 266 R P PA L S A R A 19 39 V P T K V T G I I 18 125 N P S R R P Y H F 18 152 C PQ G H A S E A 18 371 A G S G Y C G A L 17 9 F P L R A L H I V 16 81 K QR K D K V L L 16 264 A H R P P A L S A 16 279 A S P A A W L P L 16 311 GP R N P L P N P 16 271 S A R A P V P A A 15 277 P A A S P A A W L 15 322S P S G G G G L K 15 6 T K T F P L R A L 14 30 K Q D K K V D L L 14 129R P Y H F Q V P S 14 176 K Y Q A V T A T L 14 223 S P G G G S P R G 14257 T P R A G S S A H 14 276 V P A A S P A A W 14 293 R P S S C P T S S14 399 R K A E N G P H L 14 3 E H T T K T F P L 13 104 S G S F C R N K L13 110 N K L K Y L A F L 13 135 V P S R I F W R Q 13 158 S E A Y K K V CL 13 169 A P H E V G W K Y 13 224 P G G G S P R G L 13 234 F I F K T I AP L 13 237 K T I A P L A A T 13 262 S S A H R P P A L 13 280 S P A A W LP L R 13 362 V E N G R P A D L 13 378 A L W K A I E S L 13 29 M K Q D KK V D L 12 80 E K Q R K D K V L 12 107 F C R N K L K Y L 12 197 R K N KQ L M R L 12 226 G G S P R G L G F 12 249 R I G H P G G R T 12 261 G S SA H R P P A 12 267 P P A L S A R A P 12 299 T S S S T Y D S L 12 316 L PN P R H S P S 12 318 N P R H S P S G G 12 331 K P A R H C Q G Q 12 336 CQ G Q K H N V L 12 366 R P A D L A G S G 12 382 A I E S L E E G L 12 36D L L V P T K V T 11 51 A K D F G H V Q F 11 52 K D F G H V Q F V 11 186E K R K E K A E I 11 194 I H Y R K N K Q L 11 297 C P T S S S T Y D 11314 N P L P N P R H S 11 321 H S P S G G G G L 11 348 K P Q R K P K S E11 352 K P K S E N N S W 11 363 E N G R P A D L A 11 400 K A E N G P H LL 11 10 P L R A L H I V V 10 33 K K V D L L V P T 10 57 V Q F V G S Y KL 10 87 V L L G R K A V V 10 88 L L G R K A V V V 10 109 R N K L K Y L AF 10 165 C L S G A P H E V 10 270 L S A R A P V P A 10 285 L P L R T P WT R 10 289 T P W T R P S S C 10 291 W T R P S S C P T 10 325 G G G G L KK P A 10 13 A L H I V V E S I 9 21 I R D H S G Q K M 9 31 Q D K K V D LL V 9 49 Q G A K D F G H V 9 68 S N D G E H W T V 9 86 K V L L G R K A V9 95 V V S C E G I N I 9 116 A F L H K R M N T 9 127 S R R P Y H F Q V 9132 H F Q V P S R I F 9 149 G S C C P Q G H A 9 172 E V G W K Y Q A V 9173 V G W K Y Q A V T 9 175 W K Y Q A V T A T 9 195 H Y R K N K Q L M 9230 R G L G F I F K T 9 236 F K T I A P L A A 9 268 P A L S A R A P V 9275 P V P A A S P A A 9 281 P A A W L P L R T 9 337 Q G Q K H N V L A 9375 Y C G A L W K A I 9 5 T T K T F P L R A 8 8 T F P L R A L H I 8 27 QK M K Q D K K V 8 38 L V P T K V T G I 8 43 V T G I I T Q G A 8 58 Q F VG S Y K L A 8 93 A V V V S C E G I 8 156 H A S E A Y K K V 8 171 H E V GW K Y Q A 8 174 G W K Y Q A V T A 8 209 A E K N M K K K I 8 231 G L G FI F K T I 8 235 I F K T I A P L A 8 239 I A P L A A T R A 8 242 L A A TR A T R I 8 256 R T P R A G S S A 8 284 W L P L R T P W T 8 335 H C Q GQ K H N V 8 360 W Y V E N G R P A 8 374 G Y C G A L W K A 8 1 M L E H TT K T F 7 35 V D L L V P T K V 7 40 P T K V T G I I T 7 46 I I T Q G A KD F 7 85 D K V L L G R K A 7 89 L G R K A V V V S 7 99 E G I N I S G S F7 108 C R N K L K Y L A 7 114 Y L A F L H K R M 7 138 R I F W R Q E K A7 184 L E E K R K E K A 7 201 Q L M R L Q K Q A 7 213 M K K K I D K Y T7 227 G S P R G L G F I 7 232 L G F I F K T I A 7 254 G G R T P R A G S7 269 A L S A R A P V P 7 295 S S C P T S S S T 7 345 A R G K P Q R K P7 354 K S E N N S W Y V 7 370 L A G S G Y C G A 7 393 K Q K D K E R K A7 67 Y S N D G E H W T 6 79 D E K Q R K D K V 6 126 P S R R P Y H F Q 6131 Y H F Q V P S R I 6 146 A D G G S C C P Q 6 161 Y K K V C L S G A 6166 L S G A P H E V G 6 205 L Q K Q A E K N M 6 244 A T R A T R I G H 6272 A R A P V P A A S 6 283 A W L P L R T P W 6 286 P L R T P W T R P 6294 P S S C P T S S S 6 323 P S G G G G L K K 6 349 P Q R K P K S E N 6364 N G R P A D L A G 6 66 A Y S N D G E H W 5 83 R K D K V L L G R 5102 N I S G S F C R N 5 160 A Y K K V C L S G 5 222 E S P G G G S P R 5225 G G G S P R G L G 5 247 A T R I G H P G G 5 251 G H P G G R T P R 5260 A G S S A H R P P 5 273 R A P V P A A S P 5 278 A A S P A A W L P 5282 A A W L P L R T P 5 306 S L S P Y G P R N 5 313 R N P L P N P R H 5320 R H S P S G G G G 5 7 K T F P L R A L H 4 11 L R A L H I V V E 4 12R A L H I V V E S 4 23 D H S G Q K M K Q 4 34 K V D L L V P T K 4 42 K VT G I I T Q G 4 47 I T Q G A K D F G 4 59 F V G S Y K L A Y 4 90 G R K AV V V S C 4 119 H K R M N T N P S 4 145 K A D G G S C C P 4 157 A S E AY K K V C 4 163 K V C L S G A P H 4 167 S G A P H E V G W 4 216 K I D KY T E S P 4 220 Y T E S P G G G S 4 221 T E S P G G G S P 4 241 P L A AT R A T R 4 258 P R A G S S A H R 4 263 S A H R P P A L S 4 305 D S L SP Y G P R 4 315 P L P N P R H S P 4 328 G L K K P A R H C 4 338 G Q K HN V L A R 4 344 L A R G K P Q R K 4 346 R G K P Q R K P K 4 369 D L A GS G Y C G 4 384 E S L E E G L G G 4 394 Q K D K E R K A E 4 397 K E R KA E N G P 4 4 H T T K T F P L R 3 32 D K K V D L L V P 3 37 L L V P T KV T G 3 54 F G H V Q F V G S 3 60 V G S Y K L A Y S 3 69 N D G E H W T VY 3 70 D G E H W T V Y Q 3 82 Q R K D K V L L G 3 91 R K A V V V S C E 3112 L K Y L A F L H K 3 120 K R M N T N P S R 3 122 M N T N P S R R P 3123 N T N P S R R P Y 3 128 R R P Y H F Q V P 3 133 F Q V P S R I F W 3140 F W R Q E K A D G 3 144 E K A D G G S C C 3 150 S C C P Q G H A S 3159 E A Y K K V C L S 3 178 Q A V T A T L E E 3 179 A V T A T L E E K 3192 A E I H Y R K N K 3 199 N K Q L M R L Q K 3 202 L M R L Q K Q A E 3211 K N M K K K I D K 3 229 P R G L G F I F K 3 238 T I A P L A A T R 3243 A A T R A T R I G 3 246 R A T R I G H P G 3 250 I G H P G G R T P 3287 L R T P W T R P S 3 288 R T P W T R P S S 3 290 P W T R P S S C P 3298 P T S S S T Y D S 3 309 P Y G P R N P L P 3 310 Y G P R N P L P N 3319 P R H S P S G G G 3 324 S G G G G L K K P 3 326 G G G L K K P A R 3333 A R H C Q G Q K H 3 342 N V L A R G K P Q 3 356 E N N S W Y V E N 3357 N N S W Y V E N G 3 361 Y V E N G R P A D 3 368 A D L A G S G Y C 3372 G S G Y C G A L W 3 380 W K A I E S L E E 3 383 I E S L E E G L G 3386 L E E G L G G K Q 3 387 E E G L G G K Q K 3 388 E G L G G K Q K D 3389 G L G G K Q K D K 3 398 E R K A E N G P H 3 2 L E H T T K T F P 2 18V E S I R D H S G 2 20 S I R D H S G Q K 2 28 K M K Q D K K V D 2 45 G II T Q G A K D 2 48 T Q G A K D F G H 2 50 G A K D F G H V Q 2 53 D F G HV Q F V G 2 64 K L A Y S N D G E 2 78 Q D E K Q R K D K 2 97 S C E G I NI S G 2 100 G I N I S G S F C 2 103 I S G S F C R N K 2 106 S F C R N KL K Y 2 113 K Y L A F L H K R 2 124 T N P S R R P Y H 2 130 P Y H F Q VP S R 2 136 P S R I F W R Q E 2 139 I F W R Q E K A D 2 142 R Q E K A DG G S 2 143 Q E K A D G G S C 2 147 D G G S C C P Q G 2 148 G G S C C PQ G H 2 153 P Q G H A S E A Y 2 154 Q G H A S E A Y K 2 162 K K V C L SG A P 2 177 Y Q A V T A T L E 2 182 A T L E E K R K E 2 185 E E K R K EK A E 2 188 R K E K A E I H Y 2 189 K E K A E I H Y R 2 190 E K A E I HY R K 2 196 Y R K N K Q L M R 2 204 R L Q K Q A E K N 2 207 K Q A E K NM K K 2 215 K K I D K Y T E S 2 217 I D K Y T E S P G 2 233 G F I F K TI A P 2 248 T R I G H P G G R 2 253 P G G R T P R A G 2 259 R A G S S AH R P 2 265 H R P P A L S A R 2 300 S S S T Y D S L S 2 301 S S T Y D SL S P 2 303 T Y D S L S P Y G 2 304 Y D S L S P Y G P 2 312 P R N P L PN P R 2 327 G G L K K P A R H 2 329 L K K P A R H C Q 2 330 K K P A R HC Q G 2 332 P A R H C Q G Q K 2 343 V L A R G K P Q R 2 351 R K P K S EN N S 2 353 P K S E N N S W Y 2 365 G R P A D L A G S 2 367 P A D L A GS G Y 2 373 S G Y C G A L W K 2 376 C G A L W K A I E 2 390 L G G K Q KD K E 2 395 K D K E R K A E N 2 16 I V V E S I R D H 1 17 V V E S I R DH S 1 19 E S I R D H S G Q 1 22 R D H S G Q K M K 1 24 H S G Q K M K Q D1 25 S G Q K M K Q D K 1 44 T G I I T Q G A K 1 55 G H V Q F V G S Y 156 H V Q F V G S Y K 1 61 G S Y K L A Y S N 1 63 Y K L A Y S N D G 1 71G E H W T V Y Q D 1 72 E H W T V Y Q D E 1 77 Y Q D E K Q R K D 1 84 K DK V L L G R K 1 92 K A V V V S C E G 1 98 C E G I N I S G S 1 101 I N IS G S F C R 1 111 K L K Y L A F L H 1 117 F L H K R M N T N 1 118 L H KR M N T N P 1 121 R M N T N P S R R 1 137 S R I F W R Q E K 1 151 C C PQ G H A S E 1 155 G H A S E A Y K K 1 164 V C L S G A P H E 1 168 G A PH E V G W K 1 180 V T A T L E E K R 1 183 T L E E K R K E K 1 187 K R KE K A E I H 1 191 K A E I H Y R K N 1 193 E I H Y R K N K Q 1 198 K N KQ L M R L Q 1 200 K Q L M R L Q K Q 1 203 M R L Q K Q A E K 1 206 Q K QA E K N M K 1 208 Q A E K N M K K K 1 210 E K N M K K K I D 1 212 N M KK K I D K Y 1 214 K K K I D K Y T E 1 218 D K Y T E S P G G 1 219 K Y TE S P G G G 1 245 T R A T R I G H P 1 255 G R T P R A G S S 1 292 T R PS S C P T S 1 302 S T Y D S L S P Y 1 317 P N P R H S P S G 1 334 R H CQ G Q K H N 1 339 Q K H N V L A R G 1 340 K H N V L A R G K 1 341 H N VL A R G K P 1 347 G K P Q R K P K S 1 350 Q R K P K S E N N 1 355 S E NN S W Y V E 1 379 L W K A I E S L E 1 381 K A I E S L E E G 1 392 G K QK D K E R K 1

[0829] TABLE XXIX SEQ. Pos 1 2 3 4 5 6 7 8 9 score ID NO. 151P3D4 v.1:HLA Peptide Scoring Results B*08 9-mers SYFPEITHI 76 K I R I K W T K L30 164 F P R L G R Y N L 24 243 K D K S R Y D V F 24 134 Y G R Y K C E VI 23 232 V P G V R N Y G F 23 329 E A A V R F V G F 22 74 I H K I R I KW T 21 81 W T K L T S D Y L 21 336 G F P D K K H K L 21 51 S H R G G N VT L 20 241 W D K D K S R Y D 20 320 R P R R R C S P T 20 339 D K K H K LY G V 20 88 Y L K E V D V F V 19 219 I T K P R E P C G 19 123 S L V I TD L T L 18 256 N F N G R F Y Y L 18 337 F P D K K H K L Y 18 113 F L K GG S D S D 17 217 Y P I T K P R E P 17 284 A Q I A K V G Q I 17 326 S P TE A A V R F 17 58 T L P C K F Y R D 16 121 D A S L V I T D L 16 286 I AK V G Q I F A 16 293 F A A W K I L G Y 16 301 Y D R C D A G W L 16 46 QA K V F S H R G 15 146 E D D T V V V A L 15 291 Q I F A A W K I L 15 318I S R P R R R C S 15 24 L D H D R A I H I 14 33 Q A E N G P H L L 14 78R I K W T K L T S 14 86 S D Y L K E V D V 14 153 A L D L Q G V V F 14221 K P R E P C G G Q 14 245 K S R Y D V F C F 14 316 Y P I S R P R R R14 4 L L L L V L I S I 13 32 I Q A E N G P H L 13 72 S G I H K I R I K13 137 Y K C E V I E G L 13 166 R L G R Y N L N F 13 66 D P T A F G S GI 12 106 G G Y Q G R V F L 12 136 R Y K C E V I E G 12 239 G F W D K D KS R 12 267 P T K L T Y D E A 12 341 K H K L Y G V Y C 12 1 M K S L L L LV L 11 10 I S I C W A D H L 11 16 D H L S D N Y T L 11 44 A E Q A K V FS H 11 79 I K W T K L T S D 11 99 G Y H K K T Y G G 11 101 H K K T Y G GY Q 11 111 R V F L K G G S D 11 116 G G S D S D A S L 11 132 E D Y G R YK C E 11 148 D T V V V A L D L 11 159 V V F P Y F P R L 11 174 F H E A QQ A C L 11 265 I H P T K L T Y D 11 3 S L L L L V L I S 10 37 G P H L LV E A E 10 42 V E A E Q A K V F 10 60 P C K F Y R D P T 10 98 M G Y H KK T Y G 10 100 Y H K K T Y G G Y 10 107 G Y Q G R V F L K 10 186 A V I AS F D Q L 10 194 L Y D A W R G G L 10 202 L D W C N A G W L 10 262 Y Y LI H P T K L 10 272 Y D E A V Q A C L 10 285 Q I A K V G Q I F 10 295 A WK I L G Y D R 10 313 S V R Y P I S R P 10 319 S R P R R R C S P 10 338 PD K K H K L Y G 10 40 L L V E A E Q A K 9 49 V F S H R G G N V 9 61 C KF Y R D P T A 9 299 L G Y D R C D A G 9 311 D G S V R Y P I S 9 342 H KL Y G V Y C F 9 2 K S L L L L V L I 8 5 L L L V L I S I C 8 8 V L I S IC W A D 8 39 H L L V E A E Q A 8 109 Q G R V F L K G G 8 118 S D S D A SL V I 8 144 G L E D D T V V V 8 162 P Y F P R L G R Y 8 165 P R L G R YN L N 8 195 Y D A W R G G L D 8 201 G L D W C N A G W 8 211 S D G S V QY P I 8 224 E P C G G Q N T V 8 253 F T S N F N G R F 8 298 I L G Y D RC D A 8 6 L L V L I S I C W 7 17 H L S D N Y T L D 7 22 Y T L D H D R AI 7 26 H D R A I H I Q A 7 43 E A E Q A K V F S 7 55 G N V T L P C K F 762 K F Y R D P T A F 7 63 F Y R D P T A F G 7 69 A F G S G I H K I 7 71G S G I H K I R I 7 87 D Y L K E V D V F 7 105 Y G G Y Q G R V F 7 128 DL T L E D Y G R 7 155 D L Q G V V F P Y 7 156 L Q G V V F P Y F 7 161 FP Y F P R L G R 7 167 L G R Y N L N F H 7 181 C L D Q D A V I A 7 183 DQ D A V I A S F 7 209 W L S D G S V Q Y 7 234 G V R N Y G F W D 7 257 FN G R F Y Y L I 7 263 Y L I H P T K L T 7 266 H P T K L T Y D E 7 269 KL T Y D E A V Q 7 290 G Q I F A A W K I 7 308 W L A D G S V R Y 7 322 RR R C S P T E A 7 11 S I C W A D H L S 6 23 T L D H D R A I H 6 31 H I QA E N G P H 6 59 L P C K F Y R D P 6 83 K L T S D Y L K E 6 125 V I T DL T L E D 6 130 T L E D Y G R Y K 6 171 N L N F H E A Q Q 6 176 E A Q QA C L D Q 6 179 Q A C L D Q D A V 6 180 A C L D Q D A V I 6 193 Q L Y DA W R G G 6 197 A W R G G L D W C 6 249 D V F C F T S N F 6 258 N G R FY Y L I H 6 274 E A V Q A C L N D 6 277 Q A C L N D G A Q 6 278 A C L ND G A Q I 6 279 C L N D G A Q I A 6 283 G A Q I A K V G Q 6 310 A D G SV R Y P I 6 321 P R R R C S P T E 6 331 A V R F V G F P D 6 343 K L Y GV Y C F R 6 28 R A I H I Q A E N 5 73 G I H K I R I K W 5 141 V I E G LE D D T 5 152 V A L D L Q G V V 5 187 V I A S F D Q L Y 5 188 I A S F DQ L Y D 5 309 L A D G S V R Y P 5 330 A A V R F V G F P 5 9 L I S I C WA D H 4 14 W A D H L S D N Y 4 29 A I H I Q A E N G 4 68 T A F G S G I HK 4 91 E V D V F V S M G 4 97 S M G Y H K K T Y 4 140 E V I E G L E D D4 143 E G L E D D T V V 4 185 D A V I A S F D Q 4 196 D A W R G G L D W4 206 N A G W L S D G S 4 214 S V Q Y P I T K P 4 218 P I T K P R E P C4 264 L I H P T K L T Y 4 271 T Y D E A V Q A C 4 294 A A W K I L G Y D4 297 K I L G Y D R C D 4 305 D A G W L A D G S 4 317 P I S R P R R R C4 19 S D N Y T L D H D 3 120 S D A S L V I T D 3 173 N F H E A Q Q A C 3190 S F D Q L Y D A W 3 27 D R A I H I Q A E 2 35 E N G P H L L V E 2 36N G P H L L V E A 2 38 P H L L V E A E Q 2 45 E Q A K V F S H R 2 52 H RG G N V T L P 2 54 G G N V T L P C K 2 56 N V T L P C K F Y 2 70 F G S GI H K I R 2 77 I R I K W T K L T 2 84 L T S D Y L K E V 2 89 L K E V D VF V S 2 96 V S M G Y H K K T 2 126 I T D L T L E D Y 2 129 L T L E D Y GR Y 2 135 G R Y K C E V I E 2 142 I E G L E D D T V 2 145 L E D D T V VV A 2 147 D D T V V V A L D 2 151 V V A L D L Q G V 2 154 L D L Q G V VF P 2 160 V F P Y F P R L G 2 168 G R Y N L N F H E 2 169 R Y N L N F HE A 2 182 L D Q D A V I A S 2 191 F D Q L Y D A W R 2 200 G G L D W C NA G 2 215 V Q Y P I T K P R 2 227 G G Q N T V P G V 2 229 Q N T V P G VR N 2 235 V R N Y G F W D K 2 246 S R Y D V F C F T 2 251 F C F T S N FN G 2 255 S N F N G R F Y Y 2 259 G R F Y Y L I H P 2 260 R F Y Y L I HP T 2 261 F Y Y L I H P T K 2 276 V Q A C L N D G A 2 287 A K V G Q I FA A 2 332 V R F V G F P D K 2 334 F V G F P D K K H 2 335 V G F P D K KH K 2 345 Y G V Y C F R A Y 2 7 L V L I S I C W A 1 12 I C W A D H L S D1 15 A D H L S D N Y T 1 21 N Y T L D H D R A 1 25 D H D R A I H I Q 130 I H I Q A E N G P 1 50 F S H R G G N V T 1 57 V T L P C K F Y R 1 75H K I R I K W T K 1 85 T S D Y L K E V D 1 90 K E V D V F V S M 1 92 V DV F V S M G Y 1 93 D V F V S M G Y H 1 94 V F V S M G Y H K 1 95 F V S MG Y H K K 1 102 K K T Y G G Y Q G 1 110 G R V F L K G G S 1 112 V F L KG G S D S 1 115 K G G S D S D A S 1 117 G S D S D A S L V 1 119 D S D AS L V I T 1 122 A S L V I T D L T 1 131 L E D Y G R Y K C 1 133 D Y G RY K C E V 1 138 K C E V I E G L E 1 139 C E V I E G L E D 1 149 T V V VA L D L Q 1 150 V V V A L D L Q G 1 157 Q G V V F P Y F P 1 158 G V V FP Y F P R 1 170 Y N L N F H E A Q 1 175 H E A Q Q A C L D 1 184 Q D A VI A S F D 1 192 D Q L Y D A W R G 1 199 R G G L D W C N A 1 207 A G W LS D G S V 1 208 G W L S D G S V Q 1 210 L S D G S V Q Y P 1 212 D G S VQ Y P I T 1 213 G S V Q Y P I T K 1 225 P C G G Q N T V P 1 226 C G G QN T V P G 1 228 G Q N T V P G V R 1 230 N T V P G V R N Y 1 237 N Y G FW D K D K 1 240 F W D K D K S R Y 1 244 D K S R Y D V F C 1 247 R Y D VF C F T S 1 250 V F C F T S N F N 1 268 T K L T Y D E A V 1 270 L T Y DE A V Q A 1 273 D E A V Q A C L N 1 280 L N D G A Q I A K 1 281 N D G AQ I A K V 1 282 D G A Q I A K V G 1 288 K V G Q I F A A W 1 289 V G Q IF A A W K 1 292 I F A A W K I L G 1 296 W K I L G Y D R C 1 300 G Y D RC D A G W 1 303 R C D A G W L A D 1 306 A G W L A D G S V 1 307 G W L AD G S V R 1 312 G S V R Y P I S R 1 314 V R Y P I S R P R 1 323 R R C SP T E A A 1 324 R C S P T E A A V 1 327 P T E A A V R F V 1 344 L Y G VY C F R A 1 346 G V Y C F R A Y N 1 151P3D4 v.2: HLA Peptide ScoringResults B*08 9-mers SYFPEITHI 107 F C R N K L K Y L 28 109 R N K L K Y LA F 28 158 S E A Y K K V C L 24 185 E E K R K E K A E 24 80 E K Q R K DK V L 23 194 I H Y R K N K Q L 23 391 G G K Q K D K E R 23 3 E H T T K TF P L 22 187 K R K E K A E I H 22 26 G Q K M K Q D K K 21 29 M K Q D K KV D L 21 30 K Q D K K V D L L 21 82 Q R K D K V L L G 21 212 N M K K K ID K Y 21 262 S S A H R P P A L 21 395 K D K E R K A E N 21 125 N P S R RP Y H F 20 183 T L E E K R K E K 20 196 Y R K N K Q L M R 20 228 S P R GL G F I F 20 336 C Q G Q K H N V L 20 344 L A R G K P Q R K 20 350 Q R KP K S E N N 20 393 K Q K D K E R K A 20 362 V E N G R P A D L 19 79 D EK Q R K D K V 18 242 L A A T R A T R I 18 308 S P Y G P R N P L 18 389 GL G G K Q K D K 18 38 L V P T K V T G I 17 81 K Q R K D K V L L 17 88 LL G R K A V V V 17 111 K L K Y L A F L H 17 159 E A Y K K V C L S 17 209A E K N M K K K I 17 328 G L K K P A R H C 17 348 K P Q R K P K S E 17352 K P K S E N N S W 17 378 A L W K A I E S L 17 234 F I F K T I A P L16 377 G A L W K A I E S 16 8 T F P L R A L H I 15 50 G A K D F G H V Q15 87 V L L G R K A V V 15 117 F L H K R M N T N 15 186 E K R K E K A EI 15 193 E I H Y R K N K Q 15 226 G G S P R G L G F 15 252 H P G G R T PR A 15 284 W L P L R T P W T 15 231 G L G F I F K T I 14 269 A L S A R AP V P 14 271 S A R A P V P A A 14 277 P A A S P A A W L 14 289 T P W T RP S S C 14 316 L P N P R H S P S 14 382 A I E S L E E G L 14 400 K A E NG P H L L 14 1 M L E H T T K T F 13 13 A L H I V V E S I 13 39 V P T K VT G I I 13 62 S Y K L A Y S N D 13 90 G R K A V V V S C 13 172 E V G W KY Q A V 13 174 G W K Y Q A V T A 13 207 K Q A E K N M K K 13 210 E K N MK K K I D 13 257 T P R A G S S A H 13 311 G P R N P L P N P 13 326 G G GL K K P A R 13 338 G Q K H N V L A R 13 398 E R K A E N G P H 13 10 P LR A L H I V V 12 20 S I R D H S G Q K 12 24 H S G Q K M K Q D 12 46 I IT Q G A K D F 12 57 V Q F V G S Y K L 12 60 V G S Y K L A Y S 12 77 Y QD E K Q R K D 12 104 S G S F C R N K L 12 138 R I F W R Q E K A 12 141 WR Q E K A D G G 12 217 I D K Y T E S P G 12 233 G F I F K T I A P 12 286P L R T P W T R P 12 318 N P R H S P S G G 12 399 R K A E N G P H L 12 6T K T F P L R A L 11 28 K M K Q D K K V D 11 32 D K K V D L L V P 11 40P T K V T G I I T 11 84 K D K V L L G R K 11 105 G S F C R N K L K 11118 L H K R M N T N P 11 161 Y K K V C L S G A 11 189 K E K A E I H Y R11 203 M R L Q K Q A E K 11 205 L Q K Q A E K N M 11 213 M K K K I D K YT 11 215 K K I D K Y T E S 11 235 I F K T I A P L A 11 321 H S P S G G GG L 11 327 G G L K K P A R H 11 346 R G K P Q R K P K 11 371 A G S G Y CG A L 11 5 T T K T F P L R A 10 31 Q D K K V D L L V 10 48 T Q G A K D FG H 10 110 N K L K Y L A F L 10 116 A F L H K R M N T 10 143 Q E K A D GG S C 10 160 A Y K K V C L S G 10 176 K Y Q A V T A T L 10 197 R K N K QL M R L 10 198 K N K Q L M R L Q 10 211 K N M K K K I D K 10 214 K K K ID K Y T E 10 224 P G G G S P R G L 10 279 A S P A A W L P L 10 299 T S SS T Y D S L 10 329 L K K P A R H C Q 10 332 P A R H C Q G Q K 10 379 L WK A I E S L E 10 385 S L E E G L G G K 10 396 D K E R K A E N G 10 18 VE S I R D H S G 9 134 Q V P S R I F W R 9 245 T R A T R I G H P 9 255 GR T P R A G S S 9 309 P Y G P R N P L P 9 342 N V L A R G K P Q 9 347 GK P Q R K P K S 9 36 D L L V P T K V T 8 64 K L A Y S N D G E 8 89 L G RK A V V V S 8 99 E G I N I S G S F 8 124 T N P S R R P Y H 8 127 S R R PY H F Q V 8 132 H F Q V P S R I F 8 156 H A S E A Y K K V 8 169 A P H EV G W K Y 8 184 L E E K R K E K A 8 200 K Q L M R L Q K Q 8 202 L M R LQ K Q A E 8 223 S P G G G S P R G 8 267 P P A L S A R A P 8 276 V P A AS P A A W 8 280 S P A A W L P L R 8 306 S L S P Y G P R N 8 322 S P S GG G G L K 8 330 K K P A R H C Q G 8 375 Y C G A L W K A I 8 9 F P L R AL H I V 7 12 R A L H I V V E S 7 37 L L V P T K V T G 7 51 A K D F G H VQ F 7 93 A V V V S C E G I 7 95 V V S C E G I N I 7 114 Y L A F L H K RM 7 119 H K R M N T N P S 7 129 R P Y H F Q V P S 7 135 V P S R I F W RQ 7 140 F W R Q E K A D G 7 152 C P Q G H A S E A 7 165 C L S G A P H EV 7 195 H Y R K N K Q L M 7 201 Q L M R L Q K Q A 7 227 G S P R G L G FI 7 240 A P L A A T R A T 7 254 G G R T P R A G S 7 343 V L A R G K P QR 7 349 P Q R K P K S E N 7 364 N G R P A D L A G 7 381 K A I E S L E EG 7 15 H I V V E S I R D 6 92 K A V V V S C E G 6 126 P S R R P Y H F Q6 131 Y H F Q V P S R I 6 136 P S R I F W R Q E 6 168 G A P H E V G W K6 181 T A T L E E K R K 6 204 R L Q K Q A E K N 6 239 I A P L A A T R A6 241 P L A A T R A T R 6 244 A T R A T R I G H 6 247 A T R I G H P G G6 263 S A H R P P A L S 6 264 A H R P P A L S A 6 266 R P P A L S A R A6 274 A P V P A A S P A 6 285 L P L R T P W T R 6 291 W T R P S S C P T6 293 R P S S C P T S S 6 297 C P T S S S T Y D 6 314 N P L P N P R H S6 315 P L P N P R H S P 6 331 K P A R H C Q G Q 6 366 R P A D L A G S G6 369 D L A G S G Y C G 6 397 K E R K A E N G P 6 45 G I I T Q G A K D 565 L A Y S N D G E H 5 100 G I N I S G S F C 5 115 L A F L H K R M N 5178 Q A V T A T L E E 5 208 Q A E K N M K K K 5 273 R A P V P A A S P 5282 A A W L P L R T P 5 367 P A D L A G S G Y 5 16 I V V E S I R D H 496 V S C E G I N I S 4 102 N I S G S F C R N 4 145 K A D G G S C C P 4190 E K A E I H Y R K 4 191 K A E I H Y R K N 4 216 K I D K Y T E S P 4238 T I A P L A A T R 4 243 A A T R A T R I G 4 246 R A T R I G H P G 4249 R I G H P G G R T 4 259 R A G S S A H R P 4 268 P A L S A R A P V 4278 A A S P A A W L P 4 281 P A A W L P L R T 4 356 E N N S W Y V E N 4359 S W Y V E N G R P 4 370 L A G S G Y C G A 4 384 E S L E E G L G G 4387 E E G L G G K Q K 4 11 L R A L H I V V E 3 54 F G H V Q F V G S 3 73H W T V Y Q D E K 3 86 K V L L G R K A V 3 97 S C E G I N I S G 3 137 SR I F W R Q E K 3 139 I F W R Q E K A D 3 150 S C C P Q G H A S 3 167 SG A P H E V G W 3 301 S S T Y D S L S P 3 324 S G G G G L K K P 3 353 PK S E N N S W Y 3 19 E S I R D H S G Q 2 25 S G Q K M K Q D K 2 34 K V DL L V P T K 2 35 V D L L V P T K V 2 55 G H V Q F V G S Y 2 59 F V G S YK L A Y 2 68 S N D G E H W T V 2 69 N D G E H W T V Y 2 71 G E H W T V YQ D 2 72 E H W T V Y Q D E 2 91 R K A V V V S C E 2 106 S F C R N K L KY 2 144 E K A D G G S C C 2 170 P H E V G W K Y Q 2 175 W K Y Q A V T AT 2 182 A T L E E K R K E 2 219 K Y T E S P G G G 2 222 E S P G G G S PR 2 236 F K T I A P L A A 2 265 H R P P A L S A R 2 295 S S C P T S S ST 2 296 S C P T S S S T Y 2 300 S S S T Y D S L S 2 302 S T Y D S L S PY 2 313 R N P L P N P R H 2 325 G G G G L K K P A 2 337 Q G Q K H N V LA 2 341 H N V L A R G K P 2 355 S E N N S W Y V E 2 360 W Y V E N G R PA 2 363 E N G R P A D L A 2 372 G S G Y C G A L W 2 373 S G Y C G A L WK 2 383 I E S L E E G L G 2 388 E G L G G K Q K D 2 394 Q K D K E R K AE 2 4 H T T K T F P L R 1 14 L H I V V E S I R 1 17 V V E S I R D H S 121 I R D H S G Q K M 1 22 R D H S G Q K M K 1 27 Q K M K Q D K K V 1 33K K V D L L V P T 1 41 T K V T G I I T Q 1 42 K V T G I I T Q G 1 43 V TG I I T Q G A 1 44 T G I I T Q G A K 1 47 I T Q G A K D F G 1 52 K D F GH V Q F V 1 56 H V Q F V G S Y K 1 58 Q F V G S Y K L A 1 61 G S Y K L AY S N 1 70 D G E H W T V Y Q 1 74 W T V Y Q D E K Q 1 75 T V Y Q D E K QR 1 76 V Y Q D E K Q R K 1 78 Q D E K Q R K D K 1 85 D K V L L G R K A 194 V V V S C E G I N 1 98 C E G I N I S G S 1 101 I N I S G S F C R 1103 I S G S F C R N K 1 112 L K Y L A F L H K 1 120 K R M N T N P S R 1128 R R P Y H F Q V P 1 130 P Y H F Q V P S R 1 133 F Q V P S R I F W 1148 G G S C C P Q G H 1 149 G S C C P Q G H A 1 153 P Q G H A S E A Y 1155 G H A S E A Y K K 1 157 A S E A Y K K V C 1 162 K K V C L S G A P 1163 K V C L S G A P H 1 164 V C L S G A P H E 1 171 H E V G W K Y Q A 1173 V G W K Y Q A V T 1 177 Y Q A V T A T L E 1 179 A V T A T L E E K 1180 V T A T L E E K R 1 192 A E I H Y R K N K 1 199 N K Q L M R L Q K 1225 G G G S P R G L G 1 229 P R G L G F I F K 1 230 R G L G F I F K T 1237 K T I A P L A A T 1 250 I G H P G G R T P 1 251 G H P G G R T P R 1253 P G G R T P R A G 1 261 G S S A H R P P A 1 270 L S A R A P V P A 1272 A R A P V P A A S 1 275 P V P A A S P A A 1 304 Y D S L S P Y G P 1307 L S P Y G P R N P 1 334 R H C Q G Q K H N 1 335 H C Q G Q K H N V 1340 K H N V L A R G K 1 357 N N S W Y V E N G 1 358 N S W Y V E N G R 1361 Y V E N G R P A D 1 365 G R P A D L A G S 1 374 G Y C G A L W K A 1376 C G A L W K A I E 1 380 W K A I E S L E E 1 392 G K Q K D K E R K 1

[0830] TABLE XXX SEQ. Pos 1 2 3 4 5 6 7 8 9 score ID NO. 151P3D4 v.1:HLA Peptide Scoring Results B*1510 9-mers SYFPEITHI 51 S H R G G N V T L25 16 D H L S D N Y T L 21 174 F H E A Q Q A C L 21 32 I Q A E N G P H L16 106 G G Y Q G R V F L 16 146 E D D T V V V A L 15 159 V V F P Y F P RL 15 1 M K S L L L L V L 13 30 I H I Q A E N G P 13 33 Q A E N G P H L L13 74 I H K I R I K W T 13 116 G G S D S D A S L 13 137 Y K C E V I E GL 13 336 G F P D K K H K L 13 10 I S I C W A D H L 12 100 Y H K K T Y GG Y 12 121 D A S L V I T D L 12 164 F P R L G R Y N L 12 262 Y Y L I H PT K L 12 265 I H P T K L T Y D 12 272 Y D E A V Q A C L 12 341 K H K L YG V Y C 12 25 D H D R A I H I Q 11 38 P H L L V E A E Q 11 105 Y G G Y QG R V F 11 123 S L V I T D L T L 11 148 D T V V V A L D L 11 194 L Y D AW R G G L 11 202 L D W C N A G W L 11 256 N F N G R F Y Y L 11 301 Y D RC D A G W L 11 326 S P T E A A V R F 11 329 E A A V R F V G F 11 42 V EA E Q A K V F 10 76 K I R I K W T K L 10 81 W T K L T S D Y L 10 87 D YL K E V D V F 10 153 A L D L Q G V V F 10 186 A V I A S F D Q L 10 291 QI F A A W K I L 10 90 K E V D V F V S M 9 253 F T S N F N G R F 9 55 G NV T L P C K F 8 62 K F Y R D P T A F 8 156 L Q G V V F P Y F 8 243 K D KS R Y D V F 8 285 Q I A K V G Q I F 8 342 H K L Y G V Y C F 8 144 G L ED D T V V V 7 183 D Q D A V I A S F 7 232 V P G V R N Y G F 7 245 K S RY D V F C F 7 308 W L A D G S V R Y 7 317 P I S R P R R R C 7 318 I S RP R R R C S 7 43 E A E Q A K V F S 6 145 L E D D T V V V A 6 166 R L G RY N L N F 6 229 Q N T V P G V R N 6 230 N T V P G V R N Y 6 249 D V F CF T S N F 6 316 Y P I S R P R R R 6 22 Y T L D H D R A I 5 35 E N G P HL L V E 5 89 L K E V D V F V S 5 130 T L E D Y G R Y K 5 154 L D L Q G VV F P 5 209 W L S D G S V Q Y 5 217 Y P I T K P R E P 5 219 I T K P R EP C G 5 328 T E A A V R F V G 5 71 G S G I H K I R I 4 85 T S D Y L K EV D 4 88 Y L K E V D V F V 4 104 T Y G G Y Q G R V 4 118 S D S D A S L VI 4 135 G R Y K C E V I E 4 143 E G L E D D T V V 4 162 P Y F P R L G RY 4 213 G S V Q Y P I T K 4 216 Q Y P I T K P R E 4 224 E P C G G Q N TV 4 226 C G G Q N T V P G 4 228 G Q N T V P G V R 4 240 F W D K D K S RY 4 254 T S N F N G R F Y 4 264 L I H P T K L T Y 4 271 T Y D E A V Q AC 4 282 D G A Q I A K V G 4 283 G A Q I A K V G Q 4 286 I A K V G Q I FA 4 292 I F A A W K I L G 4 309 L A D G S V R Y P 4 313 S V R Y P I S RP 4 314 V R Y P I S R P R 4 315 R Y P I S R P R R 4 324 R C S P T E A AV 4 327 P T E A A V R F V 4 345 Y G V Y C F R A Y 4 17 H L S D N Y T L D3 27 D R A I H I Q A E 3 36 N G P H L L V E A 3 37 G P H L L V E A E 345 E Q A K V F S H R 3 46 Q A K V F S H R G 3 50 F S H R G G N V T 3 52H R G G N V T L P 3 54 G G N V T L P C K 3 57 V T L P C K F Y R 3 58 T LP C K F Y R D 3 59 L P C K F Y R D P 3 64 Y R D P T A F G S 3 72 S G I HK I R I K 3 73 G I H K I R I K W 3 77 I R I K W T K L T 3 84 L T S D Y LK E V 3 91 E V D V F V S M G 3 107 G Y Q G R V F L K 3 120 S D A S L V IT D 3 129 L T L E D Y G R Y 3 134 Y G R Y K C E V I 3 140 E V I E G L ED D 3 142 I E G L E D D T V 3 152 V A L D L Q G V V 3 160 V F P Y F P RL G 3 163 Y F P R L G R Y N 3 180 A C L D Q D A V I 3 181 C L D Q D A VI A 3 182 L D Q D A V I A S 3 188 I A S F D Q L Y D 3 193 Q L Y D A W RG G 3 200 G G L D W C N A G 3 208 G W L S D G S V Q 3 212 D G S V Q Y PI T 3 218 P I T K P R E P C 3 222 P R E P C G G Q N 3 225 P C G G Q N TV P 3 227 G G Q N T V P G V 3 231 T V P G V R N Y G 3 241 W D K D K S RY D 3 244 D K S R Y D V F C 3 270 L T Y D E A V Q A 3 287 A K V G Q I FA A 3 296 W K I L G Y D R C 3 297 K I L G Y D R C D 3 298 I L G Y D R CD A 3 307 G W L A D G S V R 3 311 D G S V R Y P I S 3 332 V R F V G F PD K 3 335 V G F P D K K H K 3 340 K K H K L Y G V Y 3 344 L Y G V Y C FR A 3 2 K S L L L L V L I 2 5 L L L V L I S I C 2 12 I C W A D H L S D 213 C W A D H L S D N 2 21 N Y T L D H D R A 2 23 T L D H D R A I H 2 34A E N G P H L L V 2 40 L L V E A E Q A K 2 47 A K V F S H R G G 2 61 C KF Y R D P T A 2 63 F Y R D P T A F G 2 67 P T A F G S G I H 2 68 T A F GS G I H K 2 69 A F G S G I H K I 2 70 F G S G I H K I R 2 75 H K I R I KW T K 2 78 R I K W T K L T S 2 79 I K W T K L T S D 2 86 S D Y L K E V DV 2 93 D V F V S M G Y H 2 95 F V S M G Y H K K 2 97 S M G Y H K K T Y 299 G Y H K K T Y G G 2 103 K T Y G G Y Q G R 2 110 G R V F L K G G S 2112 V F L K G G S D S 2 113 F L K G G S D S D 2 119 D S D A S L V I T 2125 V I T D L T L E D 2 126 I T D L T L E D Y 2 131 L E D Y G R Y K C 2132 E D Y G R Y K C E 2 133 D Y G R Y K C E V 2 136 R Y K C E V I E G 2138 K C E V I E G L E 2 141 V I E G L E D D T 2 147 D D T V V V A L D 2149 T V V V A L D L Q 2 155 D L Q G V V F P Y 2 157 Q G V V F P Y F P 2158 G V V F P Y F P R 2 161 F P Y F P R L G R 2 169 R Y N L N F H E A 2170 Y N L N F H E A Q 2 173 N F H E A Q Q A C 2 175 H E A Q Q A C L D 2176 E A Q Q A C L D Q 2 184 Q D A V I A S F D 2 190 S F D Q L Y D A W 2192 D Q L Y D A W R G 2 195 Y D A W R G G L D 2 197 A W R G G L D W C 2205 C N A G W L S D G 2 210 L S D G S V Q Y P 2 214 S V Q Y P I T K P 2215 V Q Y P I T K P R 2 220 T K P R E P C G G 2 221 K P R E P C G G Q 2238 Y G F W D K D K S 2 239 G F W D K D K S R 2 242 D K D K S R Y D V 2247 R Y D V F C F T S 2 255 S N F N G R F Y Y 2 261 F Y Y L I H P T K 2263 Y L I H P T K L T 2 268 T K L T Y D E A V 2 269 K L T Y D E A V Q 2273 D E A V Q A C L N 2 274 E A V Q A C L N D 2 277 Q A C L N D G A Q 2279 C L N D G A Q I A 2 280 L N D G A Q I A K 2 288 K V G Q I F A A W 2293 F A A W K I L G Y 2 299 L G Y D R C D A G 2 303 R C D A G W L A D 2304 C D A G W L A D G 2 312 G S V R Y P I S R 2 321 P R R R C S P T E 2322 R R R C S P T E A 2 323 R R C S P T E A A 2 325 C S P T E A A V R 2333 R F V G F P D K K 2 338 P D K K H K L Y G 2 346 G V Y C F R A Y N 23 S L L L L V L I S 1 7 L V L I S I C W A 1 8 V L I S I C W A D 1 9 L IS I C W A D H 1 24 L D H D R A I H I 1 28 R A I H I Q A E N 1 39 H L L VE A E Q A 1 41 L V E A E Q A K V 1 44 A E Q A K V F S H 1 48 K V F S H RG G N 1 49 V F S H R G G N V 1 56 N V T L P C K F Y 1 60 P C K F Y R D PT 1 80 K W T K L T S D Y 1 82 T K L T S D Y L K 1 96 V S M G Y H K K T 198 M G Y H K K T Y G 1 102 K K T Y G G Y Q G 1 108 Y Q G R V F L K G 1109 Q G R V F L K G G 1 114 L K G G S D S D A 1 115 K G G S D S D A S 1117 G S D S D A S L V 1 122 A S L V I T D L T 1 127 T D L T L E D Y G 1139 C E V I E G L E D 1 151 V V A L D L Q G V 1 165 P R L G R Y N L N 1167 L G R Y N L N F H 1 168 G R Y N L N F H E 1 178 Q Q A C L D Q D A 1179 Q A C L D Q D A V 1 187 V I A S F D Q L Y 1 189 A S F D Q L Y D A 1196 D A W R G G L D W 1 198 W R G G L D W C N 1 201 G L D W C N A G W 1204 W C N A G W L S D 1 223 R E P C G G Q N T 1 233 P G V R N Y G F W 1234 G V R N Y G F W D 1 235 V R N Y G F W D K 1 236 R N Y G F W D K D 1246 S R Y D V F C F T 1 248 Y D V F C F T S N 1 252 C F T S N F N G R 1259 G R F Y Y L I H P 1 260 R F Y Y L I H P T 1 266 H P T K L T Y D E 1267 P T K L T Y D E A 1 276 V Q A C L N D G A 1 281 N D G A Q I A K V 1284 A Q I A K V G Q I 1 290 G Q I F A A W K I 1 294 A A W K I L G Y D 1300 G Y D R C D A G W 1 302 D R C D A G W L A 1 310 A D G S V R Y P I 1319 S R P R R R C S P 1 330 A A V R F V G F P 1 334 F V G F P D K K H 1337 F P D K K H K L Y 1 343 K L Y G V Y C F R 1 151P3D4 v.2: HLA PeptideScoring Results B*1510 9-mers SYFPEITHI 194 I H Y R K N K Q L 22 3 E H TT K T F P L 21 6 T K T F P L R A L 15 131 Y H F Q V P S R I 15 29 M K QD K K V D L 14 81 K Q R K D K V L L 14 158 S E A Y K K V C L 14 224 P GG G S P R G L 14 251 G H P G G R T P R 14 262 S S A H R P P A L 14 399 RK A E N G P H L 14 23 D H S G Q K M K Q 13 55 G H V Q F V G S Y 13 80 EK Q R K D K V L 13 170 P H E V G W K Y Q 13 197 R K N K Q L M R L 13 264A H R P P A L S A 13 308 S P Y G P R N P L 13 320 R H S P S G G G G 13336 C Q G Q K H N V L 13 340 K H N V L A R G K 13 371 A G S G Y C G A L13 400 K A E N G P H L L 13 30 K Q D K K V D L L 12 57 V Q F V G S Y K L12 104 S G S F C R N K L 12 155 G H A S E A Y K K 12 234 F I F K T I A PL 12 277 P A A S P A A W L 12 299 T S S S T Y D S L 12 334 R H C Q G Q KH N 12 362 V E N G R P A D L 12 378 A L W K A I E S L 12 14 L H I V V ES I R 11 72 E H W T V Y Q D E 11 110 N K L K Y L A F L 11 176 K Y Q A VT A T L 11 321 H S P S G G G G L 11 382 A I E S L E E G L 11 46 I I T QG A K D F 10 107 F C R N K L K Y L 10 114 Y L A F L H K R M 10 118 L H KR M N T N P 10 132 H F Q V P S R I F 10 226 G G S P R G L G F 10 279 A SP A A W L P L 10 51 A K D F G H V Q F 9 195 H Y R K N K Q L M 9 1 M L EH T T K T F 8 21 I R D H S G Q K M 8 125 N P S R R P Y H F 8 250 I G H PG G R T P 8 99 E G I N I S G S F 7 109 R N K L K Y L A F 7 205 L Q K Q AE K N M 7 228 S P R G L G F I F 7 11 L R A L H I V V E 6 16 I V V E S IR D H 6 37 L L V P T K V T G 6 89 L G R K A V V V S 6 306 S L S P Y G PR N 6 314 N P L P N P R H S 6 361 Y V E N G R P A D 6 122 M N T N P S RR P 5 123 M T N P S R R P Y 5 167 S G A P H E V G W 5 183 T L E E K R KE K 5 190 E K A E I H Y R K 5 221 T E S P G G G S P 5 223 S P G G G S PR G 5 238 T I A P L A A T R 5 272 A R A P V P A A S 5 327 G G L K K P AR H 5 328 G L K K P A R H C 5 392 G K Q K D K E R K 5 5 T T K T F P L RA 4 12 R A L H I V V E S 4 28 K M K Q D K K V D 4 36 D L L V P T K V T 441 T K V T G I I T Q 4 47 I T Q G A K D F G 4 50 G A K D F G H V Q 4 76V Y Q D E K Q R K 4 77 Y Q D E K Q R K D 4 87 V L L G R K A V V 4 . 88 LL G R K A V V V 4 90 G R K A V V V S C 4 102 N I S G S F C R N 4 103 I SG S F C R N K 4 121 R M N T N P S R R 4 144 E K A D G G S C C 4 157 A SE A Y K K V C 4 165 C L S G A P H E V 4 174 G W K Y Q A V T A 4 182 A TL E E K R K E 4 186 E K R K E K A E I 4 198 K N K Q L M R L Q 4 208 Q AE K N M K K K 4 239 I A P L A A T R A 4 252 H P G G R T P R A 4 253 P GG R T P R A G 4 261 G S S A H R P P A 4 267 P P A L S A R A P 4 269 A LS A R A P V P 4 270 L S A R A P V P A 4 271 S A R A P V P A A 4 281 P AA W L P L R T 4 282 A A W L P L R T P 4 287 L R T P W T R P S 4 307 L SP Y G P R N P 4 313 R N P L P N P R H 4 326 G G G L K K P A R 4 338 G QK H N V L A R 4 343 V L A R G K P Q R 4 344 L A R G K P Q R K 4 345 A RG K P Q R K P 4 347 G K P Q R K P K S 4 349 P Q R K P K S E N 4 356 E NN S W Y V E N 4 360 W Y V E N G R P A 4 388 E G L G G K Q K D 4 7 K T FP L R A L H 3 15 H I V V E S I R D 3 32 D K K V D L L V P 3 33 K K V D LL V P T 3 34 K V D L L V P T K 3 54 F G H V Q F V G S 3 67 Y S N D G E HW T 3 69 N D G E H W T V Y 3 70 D G E H W T V Y Q 3 78 Q D E K Q R K D K3 84 K D K V L L G R K 3 86 K V L L G R K A V 3 91 R K A V V V S C E 396 V S C E G I N I S 3 101 I N I S G S F C R 3 115 L A F L H K R M N 3117 F L H K R M N T N 3 124 T N P S R R P Y H 3 133 F Q V P S R I F W 3135 V P S R I F W R Q 3 139 I F W R Q E K A D 3 148 G G S C C P Q G H 3150 S C C P Q G H A S 3 159 E A Y K K V C L S 3 166 L S G A P H E V G 3173 V G W K Y Q A V T 3 175 W K Y Q A V T A T 3 177 Y Q A V T A T L E 3181 T A T L E E K R K 3 184 L E E K R K E K A 3 191 K A E I H Y R K N 3220 Y T E S P G G G S 3 222 E S P G G G S P R 3 225 G G G S P R G L G 3235 I F K T I A P L A 3 240 A P L A A T R A T 3 241 P L A A T R A T R 3242 L A A T R A T R I 3 245 T R A T R I G H P 3 248 T R I G H P G G R 3249 R I G H P G G R T 3 254 G G R T P R A G S 3 255 G R T P R A G S S 3257 T P R A G S S A H 3 260 A G S S A H R P P 3 265 H R P P A L S A R 3276 V P A A S P A A W 3 278 A A S P A A W L P 3 283 A W L P L R T P W 3286 P L R T P W T R P 3 292 T R P S S C P T S 3 304 Y D S L S P Y G P 3309 P Y G P R N P L P 3 310 Y G P R N P L P N 3 311 G P R N P L P N P 3312 P R N P L P N P R 3 322 S P S G G G G L K 3 325 G G G G L K K P A 3329 L K K P A R H C Q 3 337 Q G Q K H N V L A 3 346 R G K P Q R K P K 3353 P K S E N N S W Y 3 359 S W Y V E N G R P 3 364 N G R P A D L A G 3383 I E S L E E G L G 3 385 S L E E G L G G K 3 391 G G K Q K D K E R 3393 K Q K D K E R K A 3 394 Q K D K E R K A E 3 395 K D K E R K A E N 34 H T T K T F P L R 2 10 P L R A L H I V V 2 17 V V E S I R D H S 2 24 HS G Q K M K Q D 2 25 S G Q K M K Q D K 2 42 K V T G I I T Q G 2 44 T G II T Q G A K 2 49 Q G A K D F G H V 2 52 K D F G H V Q F V 2 53 D F G H VQ F V G 2 59 F V G S Y K L A Y 2 61 G S Y K L A Y S N 2 65 L A Y S N D GE H 2 68 S N D G E H W T V 2 71 G E H W T V Y Q D 2 73 H W T V Y Q D E K2 75 T V Y Q D E K Q R 2 79 D E K Q R K D K V 2 82 Q R K D K V L L G 285 D K V L L G R K A 2 92 K A V V V S C E G 2 97 S C E G I N I S G 2 98C E G I N I S G S 2 106 S F C R N K L K Y 2 108 C R N K L K Y L A 2 127S R R P Y H F Q V 2 128 R R P Y H F Q V P 2 129 R P Y H F Q V P S 2 130P Y H F Q V P S R 2 136 P S R I F W R Q E 2 137 S R I F W R Q E K 2 140F W R Q E K A D G 2 142 R Q E K A D G G S 2 145 K A D G G S C C P 2 149G S C C P Q G H A 2 151 C C P Q G H A S E 2 152 C P Q G H A S E A 2 156H A S E A Y K K V 2 161 Y K K V C L S G A 2 164 V C L S G A P H E 2 168G A P H E V G W K 2 171 H E V G W K Y Q A 2 172 E V G W K Y Q A V 2 185E E K R K E K A E 2 188 R K E K A E I H Y 2 193 E I H Y R K N K Q 2 202L M R L Q K Q A E 2 203 M R L Q K Q A E K 2 207 K Q A E K N M K K 2 210E K N M K K K I D 2 211 K N M K K K I D K 2 212 N M K K K I D K Y 2 214K K K I D K Y T E 2 215 K K I D K Y T E S 2 217 I D K Y T E S P G 2 219K Y T E S P G G G 2 227 G S P R G L G F I 2 230 R G L G F I F K T 2 231G L G F I F K T I 2 233 G F I F K T I A P 2 236 F K T I A P L A A 2 237K T I A P L A A T 2 243 A A T R A T R I G 2 247 A T R I G H P G G 2 258P R A G S S A H R 2 259 R A G S S A H R P 2 263 S A H R P P A L S 2 266R P P A L S A R A 2 273 R A P V P A A S P 2 274 A P V P A A S P A 2 275P V P A A S P A A 2 280 S P A A W L P L R 2 285 L P L R T P W T R 2 288R T P W T R P S S 2 289 T P W T R P S S C 2 291 W T R P S S C P T 2 293R P S S C P T S S 2 294 P S S C P T S S S 2 295 S S C P T S S S T 2 303T Y D S L S P Y G 2 315 P L P N P R H S P 2 316 L P N P R H S P S 2 323P S G G G G L K K 2 324 S G G G G L K K P 2 335 H C Q G Q K H N V 2 339Q K H N V L A R G 2 350 Q R K P K S E N N 2 354 K S E N N S W Y V 2 355S E N N S W Y V E 2 357 N N S W Y V E N G 2 363 E N G R P A D L A 2 366R P A D L A G S G 2 369 D L A G S G Y C G 2 374 G Y C G A L W K A 2 375Y C G A L W K A I 2 376 C G A L W K A I E 2 377 G A L W K A I E S 2 380W K A I E S L E E 2 381 K A I E S L E E G 2 384 E S L E E G L G G 2 386L E E G L G G K Q 2 387 E E G L G G K Q K 2 389 G L G G K Q K D K 2 390L G G K Q K D K E 2 2 L E H T T K T F P 1 8 T F P L R A L H I 1 13 A L HI V V E S I 1 18 V E S I R D H S G 1 19 E S I R D H S G Q 1 20 S I R D HS G Q K 1 22 R D H S G Q K M K 1 26 G Q K M K Q D K K 1 27 Q K M K Q D KK V 1 31 Q D K K V D L L V 1 35 V D L L V P T K V 1 38 L V F T K V T G I1 39 V P T K V T G I I 1 40 P T K V T G I I T 1 45 G I I T Q G A K D 148 T Q G A K D F G H 1 58 Q F V G S Y K L A 1 60 V G S Y K L A Y S 1 63Y K L A Y S N D G 1 64 K L A Y S N D G E 1 66 A Y S N D G E H W 1 83 R KD K V L L G R 1 93 A V V V S C E G I 1 95 V V S C E G I N I 1 100 G I NI S G S F C 1 105 G S F C R N K L K 1 116 A F L H K R M N T 1 119 H K RM N T N P S 1 120 K R M N T N P S R 1 126 P S R R P Y H F Q 1 134 Q V PS R I F W R 1 141 W R Q E K A D G G 1 146 A D G G S C C P Q 1 147 D G GS C C P Q G 1 153 P Q G H A S E A Y 1 160 A Y K K V C L S G 1 162 K K VC L S G A P 1 169 A P H E V G W K Y 1 178 Q A V T A T L E E 1 179 A V TA T L E E K 1 180 V T A T L E E K R 1 187 K R K E K A E I H 1 189 K E KA E I H Y R 1 192 A E I H Y R K N K 1 196 Y R K N K Q L M R 1 199 N K QL M R L Q K 1 204 R L Q K Q A E K N 1 206 Q K Q A E K N M K 1 209 A E KN M K K K I 1 213 M K K K I D K Y T 1 216 K I D K Y T E S P 1 218 D K YT E S P G G 1 229 P R G L G F I F K 1 232 L G F I F K T I A 1 244 A T RA T R I G H 1 268 P A L S A R A P V 1 284 W L P L R T P W T 1 290 P W TR P S S C P 1 296 S C P T S S S T Y 1 298 P T S S S T Y D S 1 300 S S ST Y D S L S 1 302 S T Y D S L S P Y 1 305 D S L S P Y G P R 1 317 P N PR H S P S G 1 318 N P R H S P S G G 1 319 P R H S P S G G G 1 331 K P AR H C Q G Q 1 341 H N V L A R G K P 1 348 K P Q R K P K S E 1 351 R K PK S E N N S 1 365 G R P A D L A G S 1 368 A D L A G S G Y C 1 370 L A GS G Y C G A 1 372 G S G Y C G A L W 1 373 S G Y C G A L W K 1 396 D K ER K A E N G 1 397 K E R K A E N G P 1 398 E R K A E N G P H 1

[0831] TABLE XXXI SEQ. Pos 1 2 3 4 5 6 7 8 9 score ID NO. 151P3D4 v.1:HLA Peptide Scoring Results B*2705 9-mers SYFPEITHI 332 V R F V G F P DK 26 314 V R Y P I S R P R 25 235 V R N Y G F W D K 23 106 G G Y Q G R VF L 20 333 R F V G F P D K K 19 103 K T Y G G Y Q G R 18 135 G R Y K C EV I E 18 166 R L G R Y N L N F 18 213 G S V Q Y P I T K 18 259 G R F Y YL I H P 18 315 R Y P I S R P R R 18 322 R R R C S P T E A 18 51 S H R GG N V T L 17 55 G N V T L P C K F 17 68 T A F G S G I H K 17 76 K I R IK W T K L 17 87 D Y L K E V D V F 17 116 G G S D S D A S L 17 121 D A SL V I T D L 17 159 V V F P Y F P R L 17 168 G R Y N L N F H E 17 307 G WL A D G S V R 17 336 G F P D K K H K L 17 343 K L Y G V Y C F R 17 62 KF Y R D P T A F 16 72 S G I H K I R I K 16 75 H K I R I K W T K 16 107 GY Q G R V F L K 16 110 G R V F L K G G S 16 164 F P R L G R Y N L 16 183D Q D A V I A S F 16 239 G F W D K D K S R 16 249 D V F C F T S N F 16261 F Y Y L I H P T K 16 262 Y Y L I H P T K L 16 312 G S V R Y P I S R16 342 H K L Y G V Y C F 16 1 M K S L L L L V L 15 16 D H L S D N Y T L15 52 H R G G N V T L P 15 54 G G N V T L P C K 15 77 I R I K W T K L T15 82 T K L T S D Y L K 15 137 Y K C E V I E G L 15 158 G V V F P Y F PR 15 162 P Y F P R L G R Y 15 165 P R L G R Y N L N 15 186 A V I A S F DQ L 15 198 W R G G L D W C N 15 228 G Q N T V P G V R 15 230 N T V P G VR N Y 15 280 L N D G A Q I A K 15 290 G Q I F A A W K I 15 323 R R C S PT E A A 15 326 S P T E A A V R F 15 335 V G F P D K K H K 15 2 K S L L LL V L I 14 10 I S I C W A D H L 14 20 D N Y T L D H D R 14 45 E Q A K VF S H R 14 57 V T L P C K F Y R 14 69 A F G S G I H K I 14 80 K W T K LT S D Y 14 90 K E V D V F V S M 14 95 F V S M G Y H K K 14 123 S L V I TD L T L 14 128 D L T L E D Y G R 14 148 D T V V V A L D L 14 153 A L D LQ G V V F 14 161 F P Y F P R L G R 14 215 V Q Y P I T K P R 14 240 F W DK D K S R Y 14 272 Y D E A V Q A C L 14 308 W L A D G S V R Y 14 316 Y PI S R P R R R 14 325 C S P T E A A V R 14 340 K K H K L Y G V Y 14 4 L LL L V L I S I 13 27 D R A I H I Q A E 13 32 I Q A E N G P H L 13 42 V EA E Q A K V F 13 70 F G S G I H K I R 13 71 G S G I H K I R I 13 129 L TL E D Y G R Y 13 146 E D D T V V V A L 13 174 F H E A Q Q A C L 13 191 FD Q L Y D A W R 13 209 W L S D G S V Q Y 13 243 K D K S R Y D V F 13 245K S R Y D V F C F 13 246 S R Y D V F C F T 13 253 F T S N F N G R F 13255 S N F N G R F Y Y 13 256 N F N G R F Y Y L 13 285 Q I A K V G Q I F13 291 Q I F A A W K I L 13 293 F A A W K I L G Y 13 295 A W K I L G Y DR 13 321 P R R R C S P T E 13 14 W A D H L S D N Y 12 33 Q A E N G P H LL 12 40 L L V E A E Q A K 12 44 A E Q A K V F S H 12 64 Y R D P T A F GS 12 81 W T K L T S D Y L 12 92 V D V F V S M G Y 12 93 D V F V S M G YH 12 94 V F V S M G Y H K 12 155 D L Q G V V F P Y 12 156 L Q G V V F PY F 12 180 A C L D Q D A V I 12 222 P R E P C G G Q N 12 232 V P G V R NY G F 12 264 L I H P T K L T Y 12 284 A Q I A K V G Q I 12 289 V G Q I FA A W K 12 334 F V G F P D K K H 12 28 R A I H I Q A E N 11 67 P T A F GS G I H 11 105 Y G G Y Q G R V F 11 126 I T D L T L E D Y 11 202 L D W CN A G W L 11 237 N Y G F W D K D K 11 252 C F T S N F N G R 11 278 A C LN D G A Q I 11 301 Y D R C D A G W L 11 302 D R C D A G W L A 11 319 S RP R R R C S P 11 329 E A A V R F V G F 11 337 F P D K K H K L Y 11 31 HI Q A E N G P H 10 56 N V T L P C K F Y 10 97 S M G Y H K K T Y 10 100 YH K K T Y G G Y 10 111 R V F L K G G S D 10 130 T L E D Y G R Y K 10 167L G R Y N L N F H 10 194 L Y D A W R G G L 10 211 S D G S V Q Y P I 10236 R N Y G F W D K D 10 260 R F Y Y L I H P T 10 9 L I S I C W A D H 918 L S D N Y T L D H 9 22 Y T L D H D R A I 9 23 T L D H D R A I H 9 73G I H K I R I K W 9 118 S D S D A S L V I 9 187 V I A S F D Q L Y 9 258N G R F Y Y L I H 9 310 A D G S V R Y P I 9 345 Y G V Y C F R A Y 9 24 LD H D R A I H I 8 134 Y G R Y K C E V I 8 136 R Y K C E V I E G 8 154 LD L Q G V V F P 8 214 S V Q Y P I T K P 8 223 R E P C G G Q N T 8 224 EP C G G Q N T V 8 254 T S N F N G R F Y 8 5 L L L V L I S I C 7 66 D P TA F G S G I 7 78 R I K W T K L T S 7 99 G Y H K K T Y G G 7 112 V F L KG G S D S 7 143 E G L E D D T V V 7 199 R G G L D W C N A 7 208 G W L SD G S V Q 7 251 F C F T S N F N G 7 257 F N G R F Y Y L I 7 287 A K V GQ I F A A 7 296 W K I L G Y D R C 7 297 K I L G Y D R C D 7 303 R C D AG W L A D 7 313 S V R Y P I S R P 7 3 S L L L L V L I S 6 7 L V L I S IC W A 6 30 I H I Q A E N G P 6 37 G P H L L V E A E 6 38 P H L L V E A EQ 6 41 L V E A E Q A K V 6 53 R G G N V T L P C 6 61 C K F Y R D P T A 679 I K W T K L T S D 6 98 M G Y H K K T Y G 6 102 K K T Y G G Y Q G 6104 T Y G G Y Q G R V 6 113 F L K G G S D S D 6 140 E V I E G L E D D 6152 V A L D L Q G V V 6 169 R Y N L N F H E A 6 172 L N F H E A Q Q A 6189 A S F D Q L Y D A 6 192 D Q L Y D A W R G 6 197 A W R G G L D W C 6200 G G L D W C N A G 6 225 P C G G Q N T V P 6 238 Y G F W D K D K S 6270 L T Y D E A V Q A 6 274 E A V Q A C L N D 6 281 N D G A Q I A K V 6286 I A K V G Q I F A 6 288 K V G Q I F A A W 6 324 R C S P T E A A V 6346 G V Y C F R A Y N 6 6 L L V L I S I C W 5 15 A D H L S D N Y T 5 34A E N G P H L L V 5 39 H L L V E A E Q A 5 48 K V F S H R G G N 5 65 R DP T A F G S G 5 83 K L T S D Y L K E 5 86 S D Y L K E V D V 5 114 L K GG S D S D A 5 117 G S D S D A S L V 5 124 L V I T D L T L E 5 131 L E DY G R Y K C 5 142 I E G L E D D T V 5 144 G L E D D T V V V 5 150 V V VA L D L Q G 5 201 G L D W C N A G W 5 207 A G W L S D G S V 5 227 G G QN T V P G V 5 247 R Y D V F C F T S 5 265 I H P T K L T Y D 5 282 D G AQ I A K V G 5 283 G A Q I A K V G Q 5 294 A A W K I L G Y D 5 300 G Y DR C D A G W 5 320 R P R R R C S P T 5 8 V L I S I C W A D 4 29 A I H I QA E N G 4 35 E N G P H L L V E 4 36 N G P H L L V E A 4 43 E A E Q A K VF S 4 50 F S H R G G N V T 4 58 T L P C K F Y R D 4 74 I H K I R I K W T4 88 Y L K E V D V F V 4 96 V S M G Y H K K T 4 108 Y Q G R V F L K G 4120 S D A S L V I T D 4 122 A S L V I T D L T 4 132 E D Y G R Y K C E 4139 C E V I E G L E D 4 181 C L D Q D A V I A 4 188 I A S F D Q L Y D 4204 W C N A G W L S D 4 205 C N A G W L S D G 4 210 L S D G S V Q Y P 4216 Q Y P I T K P R E 4 217 Y P I T K P R E P 4 221 K P R E P C G G Q 4229 Q N T V P G V R N 4 231 T V P G V R N Y G 4 242 D K D K S R Y D V 4248 Y D V F C F T S N 4 266 H P T K L T Y D E 4 269 K L T Y D E A V Q 4304 C D A G W L A D G 4 306 A G W L A D G S V 4 309 L A D G S V R Y P 4338 P D K K H K L Y G 4 341 K H K L Y G V Y C 4 12 I C W A D H L S D 321 N Y T L D H D R A 3 25 D H D R A I H I Q 3 26 H D R A I H I Q A 3 46Q A K V F S H R G 3 47 A K V F S H R G G 3 85 T S D Y L K E V D 3 115 KG G S D S D A S 3 119 D S D A S L V I T 3 125 V I T D L T L E D 3 127 TD L T L E D Y G 3 138 K C E V I E G L E 3 141 V I E G L E D D T 3 145 LE D D T V V V A 3 147 D D T V V V A L D 3 173 N F H E A Q Q A C 3 175 HE A Q Q A C L D 3 176 E A Q Q A C L D Q 3 177 A Q Q A C L D Q D 3 179 QA C L D Q D A V 3 184 Q D A V I A S F D 3 190 S F D Q L Y D A W 3 196 DA W R G G L D W 3 218 P I T K P R E P C 3 219 I T K P R E P C G 3 226 CG G Q N T V P G 3 234 G V R N Y G F W D 3 263 Y L I H P T K L T 3 268 TK L T Y D E A V 3 275 A V Q A C L N D G 3 279 C L N D G A Q I A 3 292 IF A A W K I L G 3 317 P I S R P R R R C 3 330 A A V R F V G F P 3 339 DK K H K L Y G V 3 13 C W A D H L S D N 2 17 H L S D N Y T L D 2 49 V F SH R G G N V 2 59 L P C K F Y R D P 2 63 F Y R D P T A F G 2 84 L T S D YL K E V 2 89 L K E V D V F V S 2 91 E V D V F V S M G 2 133 D Y G R Y KC E V 2 149 T V V V A L D L Q 2 151 V V A L D L Q G V 2 157 Q G V V F PY F P 2 170 Y N L N F H E A Q 2 171 N L N F H E A Q Q 2 178 Q Q A C L DQ D A 2 182 L D Q D A V I A S 2 185 D A V I A S F D Q 2 193 Q L Y D A WR G G 2 206 N A G W L S D G S 2 241 W D K D K S R Y D 2 244 D K S R Y DV F C 2 250 V F C F T S N F N 2 267 P T K L T Y D E A 2 271 T Y D E A VQ A C 2 276 V Q A C L N D G A 2 277 Q A C L N D G A Q 2 299 L G Y D R CD A G 2 305 D A G W L A D G S 2 318 I S R P R R R C S 2 328 T E A A V RF V G 2 331 A V R F V G F P D 2 344 L Y G V Y C F R A 2 11 S I C W A D HL S 1 19 S D N Y T L D H D 1 109 Q G R V F L K G G 1 163 Y F P R L G R YN 1 203 D W C N A G W L S 1 212 D G S V Q Y P I T 1 220 T K P R E P C GG 1 233 P G V R N Y G F W 1 273 D E A V Q A C L N 1 298 I L G Y D R C DA 1 311 D G S V R Y P I S 1 327 P T E A A V R F V 1 151P3D4 v.2: HLAPeptide Scoring Results B*2705 9-mers SYFPEITHI 203 M R L Q K Q A E K 29120 K R M N T N P S R 25 258 P R A G S S A H R 25 196 Y R K N K Q L M R24 229 P R G L G F I F K 24 248 T R I G H P G G R 24 137 S R I F W R Q EK 23 187 K R K E K A E I H 23 265 H R P P A L S A R 23 312 P R N P L P NP R 23 21 I R D H S G Q K M 22 333 A R H C Q G Q K H 21 197 R K N K Q LM R L 20 398 E R K A E N G P H 20 57 V Q F V G S Y K L 19 83 R K D K V LL G R 19 234 F I F K T I A P L 19 251 G H P G G R T P R 19 327 G G L K KP A R H 19 22 R D H S G Q K M K 18 26 G Q K M K Q D K K 18 155 G H A S EA Y K K 18 207 K Q A E K N M K K 18 313 R N P L P N P R H 18 345 A R G KP Q R K P 18 389 G L G G K Q K D K 18 391 G G K Q K D K E R 18 392 G K QK D K E R K 18 34 K V D L L V P T K 17 90 G R K A V V V S C 17 105 G S FC R N K L K 17 109 R N K L K Y L A F 17 113 K Y L A F L H K R 17 121 R MN T N P S R R 17 211 K N M K K K I D K 17 323 P S G G G G L K K 17 326 GG G L K K P A R 17 378 A L W K A I E S L 17 7 K T F P L R A L H 16 11 LR A L H I V V E 16 30 K Q D K K V D L L 16 46 I I T Q G A K D F 16 55 GH V Q F V G S Y 16 81 K Q R K D K V L L 16 84 K D K V L L G R K 16 101 IN I S G S F C R 16 110 N K L K Y L A F L 16 189 K E K A E I H Y R 16 194I H Y R K N K Q L 16 212 N M K K K I D K Y 16 255 G R T P R A G S S 16308 S P Y G P R N P L 16 373 S G Y C G A L W K 16 399 R K A E N G P H L16 16 I V V E S I R D H 15 51 A K D F G H V Q F 15 75 T V Y Q D E K Q R15 99 E G I N I S G S F 15 108 C R N K L K Y L A 15 128 R R P Y H F Q VP 15 131 Y H F Q V P S R I 15 168 G A P H E V G W K 15 176 K Y Q A V T AT L 15 188 R K E K A E I H Y 15 190 E K A E I H Y R K 15 192 A E I H Y RK N K 15 222 E S P G G G S P R 15 226 G G S P R G L G F 15 238 T I A P LA A T R 15 336 C Q G Q K H N V L 15 338 G Q K H N V L A R 15 343 V L A RG K P Q R 15 344 L A R G K P Q R K 15 346 R G K P Q R K P K 15 350 Q R KP K S E N N 15 365 G R P A D L A G S 15 14 L H I V V E S I R 14 44 T G II T Q G A K 14 76 V Y Q D E K Q R K 14 112 L K Y L A F L H K 14 169 A PH E V G W K Y 14 181 T A T L E E K R K 14 208 Q A E K N M K K K 14 272 AR A P V P A A S 14 285 L P L R T P W T R 14 322 S P S G G G G L K 14 340K H N V L A R G K 14 385 S L E E G L G G K 14 387 E E G L G G K Q K 14400 K A E N G P H L L 14 4 H T T K T F P L R 13 25 S G Q K M K Q D K 1329 M K Q D K K V D L 13 73 H W T V Y Q D E K 13 80 E K Q R K D K V L 1382 Q R K D K V L L G 13 103 I S G S F C R N K 13 104 S G S F C R N K L13 130 P Y H F Q V P S R 13 134 Q V P S R I F W R 13 141 W R Q E K A D GG 13 158 S E A Y K K V C L 13 163 K V C L S G A P H 13 179 A V T A T L EE K 13 180 V T A T L E E K R 13 183 T L E E K R K E K 13 199 N K Q L M RL Q K 13 206 Q K Q A E K N M K 13 224 P G G G S P R G L 13 228 S P R G LG F I F 13 230 R G L G F I F K T 13 245 T R A T R I G H P 13 277 P A A SP A A W L 13 292 T R P S S C P T S 13 302 S T Y D S L S P Y 13 305 D S LS P Y G P R 13 332 P A R H C Q G Q K 13 362 V E N G R P A D L 13 371 A GS G Y C G A L 13 6 T K T F P L R A L 12 20 S I R D H S G Q K 12 56 H V QF V G S Y K 12 65 L A Y S N D G E H 12 69 N D G E H W T V Y 12 78 Q D EK Q R K D K 12 106 S F C R N K L K Y 12 107 F C R N K L K Y L 12 111 K LK Y L A F L H 12 127 S R R P Y H F Q V 12 132 H F Q V P S R I F 12 154 QG H A S E A Y K 12 186 E K R K E K A E I 12 205 L Q K Q A E K N M 12 227G S P R G L G F I 12 241 P L A A T R A T R 12 257 T P R A G S S A H 12279 A S P A A W L P L 12 280 S P A A W L P L R 12 296 S C P T S S S T Y12 319 P R H S P S G G G 12 321 H S P S G G G G L 12 358 N S W Y V E N GR 12 382 A I E S L E E G L 12 1 M L E H T T K T F 11 3 E H T T K T F P L11 42 K V T G I I T Q G 11 61 G S Y K L A Y S N 11 114 Y L A F L H K R M11 125 N P S R R P Y H F 11 138 R I F W R Q E K A 11 148 G G S C C P Q GH 11 195 H Y R K N K Q L M 11 231 G L G F I F K T I 11 242 L A A T R A TR I 11 262 S S A H R P P A L 11 287 L R T P W T R P S 11 299 T S S S T YD S L 11 353 P K S E N N S W Y 11 12 R A L H I V V E S 10 13 A L H I V VE S I 10 38 L V P T K V T G I 10 48 T Q G A K D F G H 10 59 F V G S Y KL A Y 10 95 V V S C E G I N I 10 123 N T N P S R R P Y 10 209 A E K N MK K K I 10 244 A T R A T R I G H 10 334 R H C Q G Q K H N 10 351 R K P KS E N N S 10 367 P A D L A G S G Y 10 8 T F P L R A L H I 9 39 V P T K VT G I I 9 93 A V V V S C E G I 9 124 T N P S R R P Y H 9 129 R P Y H F QV P S 9 153 P Q G H A S E A Y 9 204 R L Q K Q A E K N 9 266 R P P A L SA R A 9 347 G K P Q R K P K S 9 374 G Y C G A L W K A 9 377 G A L W K AI E S 9 388 E G L G G K Q K D 9 35 V D L L V P T K V 8 41 T K V T G I IT Q 8 45 G I I T Q G A K D 8 52 K D F G H V Q F V 8 182 A T L E E K R KE 8 215 K K I D K Y T E S 8 223 S P G G G S P R G 8 259 R A G S S A H RP 8 273 R A P V P A A S P 8 311 G P R N P L P N P 8 381 K A I E S L E EG 8 86 K V L L G R K A V 7 87 V L L G R K A V V 7 91 R K A V V V S C E 796 V S C E G I N I S 7 116 A F L H K R M N T 7 142 R Q E K A D G G S 7145 K A D G G S C C P 7 175 W K Y Q A V T A T 7 200 K Q L M R L Q K Q 7233 G F I F K T I A P 7 237 K T I A P L A A T 7 239 I A P L A A T R A 7249 R I G H P G G R T 7 283 A W L P L R T P W 7 293 R P S S C P T S S 7324 S G G G G L K K P 7 325 G G G G L K K P A 7 328 G L K K P A R H C 7366 R P A D L A G S G 7 375 Y C G A L W K A I 7 15 H I V V E S I R D 623 D H S G Q K M K Q 6 28 K M K Q D K K V D 6 33 K K V D L L V P T 6 71G E H W T V Y Q D 6 77 Y Q D E K Q R K D 6 92 K A V V V S C E G 6 97 S CE G I N I S G 6 149 G S C C P Q G H A 6 151 C C P Q G H A S E 6 159 E AY K K V C L S 6 160 A Y K K V C L S G 6 164 V C L S G A P H E 6 171 H EV G W K Y Q A 6 173 V G W K Y Q A V T 6 174 G W K Y Q A V T A 6 232 L GF I F K T I A 6 256 R T P R A G S S A 6 264 A H R P P A L S A 6 288 R TP W T R P S S 6 320 R H S P S G G G G 6 349 P Q R K P K S E N 6 352 K PK S E N N S W 6 359 S W Y V E N G R P 6 368 A D L A G S G Y C 6 395 K DK E R K A E N 6 27 Q K M K Q D K K V 5 31 Q D K K V D L L V 5 37 L L V PT K V T G 5 68 S N D G E H W T V 5 79 D E K Q R K D K V 5 85 D K V L L GR K A 5 89 L G R K A V V V S 5 100 G I N I S G S F C 5 102 N I S G S F CR N 5 115 L A F L H K R M N 5 118 L H K R M N T N P 5 140 F W R Q E K AD G 5 152 C P Q G H A S E A 5 162 K K V C L S G A P 5 184 L E E K R K EK A 5 198 K N K Q L M R L Q 5 214 K K K I D K Y T E 5 216 K I D K Y T ES P 5 218 D K Y T E S P G G 5 246 R A T R I G H P G 5 250 I G H P G G RT P 5 252 H P G G R T P R A 5 254 G G R T P R A G S 5 274 A P V P A A SP A 5 282 A A W L P L R T P 5 286 P L R T P W T R P 5 335 H C Q G Q K HN V 5 339 Q K H N V L A R G 5 384 E S L E E G L G G 5 386 L E E G L G GK Q 5 390 L G G K Q K D K E 5 393 K Q K D K E R K A 5 397 K E R K A E NG P 5 24 H S G Q K M K Q D 4 36 D L L V P T K V T 4 47 I T Q G A K D F G4 50 G A K D F G H V Q 4 53 D F G H V Q F V G 4 58 Q F V G S Y K L A 462 S Y K L A Y S N D 4 63 Y K L A Y S N D G 4 64 K L A Y S N D G E 4 74W T V Y Q D E K Q 4 88 L L G R K A V V V 4 98 C E G I N I S G S 4 117 FL H K R M N T N 4 122 M N T N P S R R P 4 133 F Q V P S R I F W 4 135 VP S R I F W R Q 4 146 A D G G S C C P Q 4 191 K A E I H Y R K N 4 193 EI H Y R K N K Q 4 201 Q L M R L Q K Q A 4 213 M K K K I D K Y T 4 219 KY T E S P G G G 4 221 T E S P G G G S P 4 225 G G G S P R G L G 4 235 IF K T I A P L A 4 247 A T R I G H P G G 4 261 G S S A H R P P A 4 269 AL S A R A P V P 4 278 A A S P A A W L P 4 281 P A A W L P L R T 4 295 SS C P T S S S T 4 297 C P T S S S T Y D 4 306 S L S P Y G P R N 4 307 LS P Y G P R N P 4 337 Q G Q K H N V L A 4 341 H N V L A R G K P 4 348 KP Q R K P K S E 4 354 K S E N N S W Y V 4 369 D L A G S G Y C G 4 372 GS G Y C G A L W 4 380 W K A I E S L E E 4 396 D K E R K A E N G 4 2 L EH T T K T F P 3 5 T T K T F P L R A 3 9 F P L R A L H I V 3 10 P L R A LH I V V 3 19 E S I R D H S G Q 3 32 D K K V D L L V P 3 60 V G S Y K L AY S 3 144 E K A D G G S C C 3 156 H A S E A Y K K V 3 157 A S E A Y K KV C 3 165 C L S G A P H E V 3 177 Y Q A V T A T L E 3 178 Q A V T A T LE E 3 240 A P L A A T R A T 3 267 P P A L S A R A P 3 268 P A L S A R AP V 3 271 S A R A P V P A A 3 290 P W T R P S S C P 3 291 W T R P S S CP T 3 294 P S S C P T S S S 3 301 S S T Y D S L S P 3 303 T Y D S L S PY G 3 304 Y D S L S P Y G P 3 309 P Y G P R N P L P 3 314 N P L P N P RH S 3 317 P N P R H S P S G 3 330 K K P A R H C Q G 3 355 S E N N S W YV E 3 357 N N S W Y V E N G 3 361 Y V E N G R P A D 3 364 N G R P A D LA G 3 376 C G A L W K A I E 3 383 I E S L E E G L G 3 394 Q K D K E R KA E 3 18 V E S I R D H S G 2 49 Q G A K D F G H V 2 67 Y S N D G E H W T2 147 D G G S C C P Q G 2 161 Y K K V C L S G A 2 166 L S G A P H E V G2 167 S G A P H E V G W 2 170 P H E V G W K Y Q 2 202 L M R L Q K Q A E2 210 E K N M K K K I D 2 217 I D K Y T E S P G 2 263 S A H R P P A L S2 275 P V P A A S P A A 2 276 V P A A S P A A W 2 284 W L P L R T P W T2 289 T P W T R P S S C 2 298 P T S S S T Y D S 2 300 S S S T Y D S L S2 315 P L P N P R H S P 2 316 L P N P R H S P S 2 318 N P R H S P S G G2 331 K P A R H C Q G Q 2 342 N V L A R G K P Q 2 356 E N N S W Y V E N2 360 W Y V E N G R P A 2 363 E N G R P A D L A 2 370 L A G S G Y C G A2 379 L W K A I E S L E 2 17 V V E S I R D H S 1 40 P T K V T G I I T 143 V T G I I T Q G A 1 54 F G H V Q F V G S 1 66 A Y S N D G E H W 1 70D G E H W T V Y Q 1 72 E H W T V Y Q D E 1 94 V V V S C E G I N 1 119 HK R M N T N P S 1 126 P S R R P Y H F Q 1 136 P S R I F W R Q E 1 139 IF W R Q E K A D 1 143 Q E K A D G G S C 1 150 S C C P Q G H A S 1 172 EV G W K Y Q A V 1 185 E E K R K E K A E 1 220 Y T E S P G G G S 1 236 FK T I A P L A A 1 243 A A T R A T R I G 1 260 A G S S A H R P P 1 270 LS A R A P V P A 1 310 Y G P R N P L P N 1 329 L K K P A R H C Q 1

[0832] TABLE XXXII SEQ. Pos 1 2 3 4 5 6 7 8 9 score ID NO. 151P364 v.1:HLA Peptide Scoring Results B*2709 9-mers SYFPEITHI 106 G G Y Q G R V FL 16 135 G R Y K C E V I E 16 16 D H L S D N Y T L 15 159 V V F P Y F PR L 15 168 G R Y N L N F H E 15 259 G R F Y Y L I H P 15 323 R R C S P TE A A 15 110 G R V F L K G G S 14 117 G S D S D A S L V 14 166 R L G R YN L N F 14 314 V R Y P I S R P R 14 322 R R R C S P T E A 14 2 K S L L LL V L I 13 10 I S I C W A D H L 13 62 K F Y R D P T A F 13 116 G G S D SD A S L 13 144 G L E D D T V V V 13 148 D T V V V A L D L 13 186 A V I AS F D Q L 13 227 G G Q N T V P G V 13 278 A C L N D G A Q I 13 290 G Q IF A A W K I 13 324 R C S P T E A A V 13 332 V R F V G F P D K 13 336 G FP D K K H K L 13 32 I Q A E N G P H L 12 55 G N V T L P C K F 12 64 Y RD P T A F G S 12 71 G S G I H K I R I 12 76 K I R I K W T K L 12 77 I RI K W T K L T 12 90 K E V D V F V S M 12 123 S L V I T D L T L 12 146 ED D T V V V A L 12 164 F P R L G R Y N L 12 165 P R L G R Y N L N 12 222P R E P C G G Q N 12 245 K S R Y D V F C F 12 246 S R Y D V F C F T 12262 Y Y L I H P T K L 12 284 A Q I A K V G Q I 12 291 Q I F A A W K I L12 301 Y D R C D A G W L 12 326 S P T E A A V R F 12 342 H K L Y G V Y CF 12 1 M K S L L L L V L 11 51 S H R G G N V T L 11 52 H R G G N V T L P11 86 S D Y L K E V D V 11 87 D Y L K E V D V F 11 143 E G L E D D T V V11 180 A C L D Q D A V I 11 202 L D W C N A G W L 11 243 K D K S R Y D VF 11 249 D V F C F T S N F 11 256 N F N G R F Y Y L 11 310 A D G S V R YP I 11 321 P R R R C S P T E 11 4 L L L L V L I S I 10 22 Y T L D H D RA I 10 27 D R A I H I Q A E 10 33 Q A E N G P H L L 10 34 A E N G P H LL V 10 69 A F G S G I H K I 10 81 W T K L T S D Y L 10 121 D A S L V I TD L 10 137 Y K C E V I E G L 10 152 V A L D L Q G V V 10 153 A L D L Q GV V F 10 174 F H E A Q Q A C L 10 194 L Y D A W R G G L 10 198 W R G G LD W C N 10 211 S D G S V Q Y P I 10 235 V R N Y G F W D K 10 268 T K L TY D E A V 10 272 Y D E A V Q A C L 10 302 D R C D A G W L A 10 319 S R PR R R C S P 10 24 L D H D R A I H I 9 42 V E A E Q A K V F 9 49 V F S HR G G N V 9 66 D P T A F G S G I 9 88 Y L K E V D V F V 9 104 T Y G G YQ G R V 9 118 S D S D A S L V I 9 142 I E G L E D D T V 9 151 V V A L DL Q G V 9 156 L Q G V V F P Y F 9 179 Q A C L D Q D A V 9 207 A G W L SD G S V 9 232 V P G V R N Y G F 9 242 D K D K S R Y D V 9 253 F T S N FN G R F 9 257 F N G R F Y Y L I 9 306 A G W L A D G S V 9 327 P T E A AV R F V 9 329 E A A V R F V G F 9 339 D K K H K L Y G V 9 41 L V E A E QA K V 8 84 L T S D Y L K E V 8 105 Y G G Y Q G R V F 8 133 D Y G R Y K CE V 8 134 Y G R Y K C E V I 8 183 D Q D A V I A S F 8 224 E P C G G Q NT V 8 281 N D G A Q I A K V 8 285 Q I A K V G Q I F 8 208 G W L S D G SV Q 7 28 R A I H I Q A E N 6 83 K L T S D Y L K E 6 111 R V F L K G G SD 6 199 R G G L D W C N A 6 236 R N Y G F W D K D 6 260 R F Y Y L I H PT 6 307 G W L A D G S V R 6 315 R Y P I S R P R R 6 48 K V F S H R G G N5 53 R G G N V T L P C 5 78 R I K W T K L T S 5 102 K K T Y G G Y Q G 5136 R Y K C E V I E G 5 192 D Q L Y D A W R G 5 200 G G L D W C N A G 5223 R E P C G G Q N T 5 270 L T Y D E A V Q A 5 303 R C D A G W L A D 5333 R F V G F P D K K 5 346 G V Y C F R A Y N 5 3 S L L L L V L I S 4 37G P H L L V E A E 4 39 H L L V E A E Q A 4 54 G G N V T L P C K 4 65 R DP T A F G S G 4 73 G I H K I R I K W 4 99 G Y H K K T Y G G 4 103 K T YG G Y Q G R 4 107 G Y Q G R V F L K 4 115 K G G S D S D A S 4 122 A S LV I T D L T 4 129 L T L E D Y G R Y 4 154 L D L Q G V V F P 4 158 G V VF P Y F P R 4 162 P Y F P R L G R Y 4 169 R Y N L N F H E A 4 172 L N FH E A Q Q A 4 189 A S F D Q L Y D A 4 213 G S V Q Y P I T K 4 215 V Q YP I T K P R 4 230 N T V P G V R N Y 4 247 R Y D V F C F T S 4 261 F Y YL I H P T K 4 269 K L T Y D E A V Q 4 283 G A Q I A K V G Q 4 297 K I LG Y D R C D 4 312 G S V R Y P I S R 4 320 R P R R R C S P T 4 335 V G FP D K K H K 4 343 K L Y G V Y C F R 4 8 V L I S I C W A D 3 12 I C W A DH L S D 3 21 N Y T L D H D R A 3 29 A I H I Q A E N G 3 57 V T L P C K FY R 3 61 C K F Y R D P T A 3 80 K W T K L T S D Y 3 82 T K L T S D Y L K3 94 V F V S M G Y H K 3 138 K C E V I E G L E 3 150 V V V A L D L Q G 3161 F P Y F P R L G R 3 181 C L D Q D A V I A 3 188 I A S F D Q L Y D 3201 G L D W C N A G W 3 219 I T K P R E P C G 3 228 G Q N T V P G V R 3229 Q N T V P G V R N 3 234 G V R N Y G F W D 3 238 Y G F W D K D K S 3239 G F W D K D K S R 3 251 F C F T S N F N G 3 274 E A V Q A C L N D 3288 K V G Q I F A A W 3 300 G Y D R C D A G W 3 316 Y P I S R P R R R 3330 A A V R F V G F P 3 341 K H K L Y G V Y C 3 5 L L L V L I S I C 2 6L L V L I S I C W 2 7 L V L I S I C W A 2 20 D N Y T L D H D R 2 26 H DR A I H I Q A 2 30 I H I Q A E N G P 2 35 E N G P H L L V E 2 38 P H L LV E A E Q 2 44 A E Q A K V F S H 2 47 A K V F S H R G G 2 58 T L P C K FY R D 2 68 T A F G S G I H K 2 75 H K I R I K W T K 2 89 L K E V D V F VS 2 93 D V F V S M G Y H 2 98 M G Y H K K T Y G 2 112 V F L K G G S D S2 120 S D A S L V I T D 2 124 L V I T D L T L E 2 125 V I T D L T L E D2 127 T D L T L E D Y G 2 128 D L T L E D Y G R 2 132 E D Y G R Y K C E2 139 C E V I E G L E D 2 145 L E D D T V V V A 2 147 D D T V V V A L D2 157 Q G V V F P Y F P 2 170 Y N L N F H E A Q 2 177 A Q Q A C L D Q D2 184 Q D A V I A S F D 2 193 Q L Y D A W R G G 2 209 W L S D G S V Q Y2 216 Q Y P I T K P R E 2 221 K P R E P C G G Q 2 240 F W D K D K S R Y2 252 C F T S N F N G R 2 255 S N F N G R F Y Y 2 264 L I H P T K L T Y2 266 H P T K L T Y D E 2 282 D G A Q I A K V G 2 287 A K V G Q I F A A2 294 A A W K I L G Y D 2 295 A W K I L G Y D R 2 296 W K I L G Y D R C2 298 I L G Y D R C D A 2 299 L G Y D R C D A G 2 308 W L A D G S V R Y2 318 I S R P R R R C S 2 340 K K H K L Y G V Y 2 14 W A D H L S D N Y 115 A D H L S D N Y T 1 18 L S D N Y T L D H 1 23 T L D H D R A I H 1 36N G P H L L V E A 1 40 L L V E A E Q A K 1 43 E A E Q A K V F S 1 46 Q AK V F S H R G 1 56 N V T L P C K F Y 1 70 F G S G I H K I R 1 72 S G I HK I R I K 1 74 I H K I R I K W T 1 79 I K W T K L T S D 1 91 E V D V F VS M G 1 92 V D V F V S M G Y 1 108 Y Q G R V F L K G 1 119 D S D A S L VI T 1 126 I T D L T L E D Y 1 131 L E D Y G R Y K C 1 140 E V I E G L ED D 1 149 T V V V A L D L Q 1 155 D L Q G V V F P Y 1 171 N L N F H E AQ Q 1 175 H E A Q Q A C L D 1 176 E A Q Q A C L D Q 1 182 L D Q D A V IA S 1 185 D A V I A S F D Q 1 187 V I A S F D Q L Y 1 196 D A W R G G LD W 1 197 A W R G G L D W C 1 204 W C N A G W L S D 1 210 L S D G S V QY P 1 212 D G S V Q Y P I T 1 217 Y P I T K P R E P 1 218 P I T K P R EP C 1 226 C G G Q N T V P G 1 233 P G V R N Y G F W 1 244 D K S R Y D VF C 1 248 Y D V F C F T S N 1 258 N G R F Y Y L I H 1 263 Y L I H P T KL T 1 265 I H P T K L T Y D 1 271 T Y D E A V Q A C 1 273 D E A V Q A CL N 1 275 A V Q A C L N D G 1 279 C L N D G A Q I A 1 286 I A K V G Q IF A 1 289 V G Q I F A A W K 1 292 I F A A W K I L G 1 293 F A A W K I LG Y 1 305 D A G W L A D G S 1 309 L A D G S V R Y P 1 311 D G S V R Y PI S 1 313 S V R Y P I S R P 1 317 P I S R P R R R C 1 325 C S P T E A AV R 1 331 A V R F V G F P D 1 338 P D K K H K L Y G 1 344 L Y G V Y C FR A 1 345 Y G V Y C F R A Y 1 151P3D4 v.2: HLA Peptide Scoring ResultsB*2709 9-mers SYFPEITHI 127 S R R P Y H F Q V 20 21 I R D H S G Q K M 19255 G R T P R A G S S 16 90 G R K A V V V S C 15 197 R K N K Q L M R L15 399 R K A E N G P H L 15 81 K Q R K D K V L L 14 128 R R P Y H F Q VP 14 194 I H Y R K N K Q L 14 365 G R P A D L A G S 14 30 K Q D K K V DL L 13 52 K D F G H V Q F V 13 57 V Q F V G S Y K L 13 109 R N K L K Y LA F 13 120 K R M N T N P S R 13 187 K R K E K A E I H 13 226 G G S P R GL G F 13 82 Q R K D K V L L G 12 86 K V L L G R K A V 12 110 N K L K Y LA F L 12 176 K Y Q A V T A T L 12 203 M R L Q K Q A E K 12 231 G L G F IF K T I 12 234 F I F K T I A P L 12 272 A R A P V P A A S 12 277 P A A SP A A W L 12 279 A S P A A W L P L 12 287 L R T P W T R P S 12 292 T R PS S C P T S 12 308 S P Y G P R N P L 12 350 Q R K P K S E N N 12 382 A IE S L E E G L 12 400 K A E N G P H L L 12 3 E H T T K T F P L 11 6 T K TF P L R A L 11 11 L R A L H I V V E 11 29 M K Q D K K V D L 11 46 I I TQ G A K D F 11 51 A K D F G H V Q F 11 108 C R N K L K Y L A 11 131 Y HF Q V P S R I 11 137 S R I F W R Q E K 11 141 W R Q E K A D G G 11 158 SE A Y K K V C L 11 196 Y R K N K Q L M R 11 227 G S P R G L G F I 11 248T R I G H P G G R 11 262 S S A H R P P A L 11 265 H R P P A L S A R 11268 P A L S A R A P V 11 299 T S S S T Y D S L 11 312 P R N P L P N P R11 319 P R H S P S G G G 11 321 H S P S G G G G L 11 333 A R H C Q G Q KH 11 345 A R G K P Q R K P 11 371 A G S G Y C G A L 11 378 A L W K A I ES L 11 8 T F P L R A L H I 10 9 F P L R A L H I V 10 13 A L H I V V E SI 10 35 V D L L V P T K V 10 80 E K Q R K D K V L 10 87 V L L G R K A VV 10 88 L L G R K A V V V 10 93 A V V V S C E G I 10 99 E G I N I S G SF 10 104 S G S F C R N K L 10 107 F C R N K L K Y L 10 224 P G G G S P RG L 10 229 P R G L G F I F K 10 242 L A A T R A T R I 10 245 T R A T R IG H P 10 258 P R A G S S A H R 10 336 C Q G Q K H N V L 10 354 K S E N NS W Y V 10 362 V E N G R P A D L 10 398 E R K A E N G P H 10 12 R A L HI V V E S 9 31 Q D K K V D L L V 9 38 L V P T K V T G I 9 39 V P T K V TG I I 9 49 Q G A K D F G H V 9 95 V V S C E G I N I 9 114 Y L A F L H KR M 9 125 N P S R R P Y H F 9 205 L Q K Q A E K N M 9 209 A E K N M K KK I 9 335 H C Q G Q K H N V 9 1 M L E H T T K T F 8 10 P L R A L H I V V8 27 Q K M K Q D K K V 8 68 S N D G E H W T V 8 79 D E K Q R K D K V 8132 H F Q V P S R I F 8 156 H A S E A Y K K V 8 165 C L S G A P H E V 8172 E V G W K Y Q A V 8 186 E K R K E K A E I 8 195 H Y R K N K Q L M 8228 S P R G L G F I F 8 375 Y C G A L W K A I 8 61 G S Y K L A Y S N 7129 R P Y H F Q V P S 7 259 R A G S S A H R P 7 71 G E H W T V Y Q D 6138 R I F W R Q E K A 6 155 G H A S E A Y K K 6 230 R G L G F I F K T 6246 R A T R I G H P G 6 313 R N P L P N P R H 6 327 G G L K K P A R H 6377 G A L W K A I E S 6 7 K T F P L R A L H 5 22 R D H S G Q K M K 5 42K V T G I I T Q G 5 55 G H V Q F V G S Y 5 83 R K D K V L L G R 5 91 R KA V V V S C E 5 105 G S F C R N K L K 5 121 R M N T N P S R R 5 164 V CL S G A P H E 5 174 G W K Y Q A V T A 5 204 R L Q K Q A E K N 5 249 R IG H P G G R T 5 266 R P P A L S A R A 5 273 R A P V P A A S P 5 288 R TP W T R P S S 5 293 R P S S C P T S S 5 311 G P R N P L P N P 5 320 R HS P S G G G G 5 338 G Q K H N V L A R 5 346 R G K P Q R K P K 5 351 R KP K S E N N S 5 366 R P A D L A G S G 5 392 G K Q K D K E R K 5 33 K K VD L L V P T 4 34 K V D L L V P T K 4 45 G I I T Q G A K D 4 75 T V Y Q DE K Q R 4 113 K Y L A F L H K R 4 116 A F L H K R M N T 4 142 R Q E K AD G G S 4 168 G A P H E V G W K 4 188 R K E K A E I H Y 4 200 K Q L M RL Q K Q 4 214 K K K I D K Y T E 4 225 G G G S P R G L G 4 233 G F I F KT I A P 4 235 I F K T I A P L A 4 256 R T P R A G S S A 4 261 G S S A HR P P A 4 264 A H R P P A L S A 4 274 A P V P A A S P A 4 283 A W L P LR T P W 4 326 G G G L K K P A R 4 328 G L K K P A R H C 4 334 R H C Q GQ K H N 4 347 G K P Q R K P K S 4 373 S G Y C G A L W K 4 26 G Q K M K QD K K 3 28 K M K Q D K K V D 3 37 L L V P T K V T G 3 50 G A K D F G H VQ 3 65 L A Y S N D G E H 3 84 K D K V L L G R K 3 92 K A V V V S C E G 3100 G I N I S G S F C 3 101 I N I S G S F C R 3 103 I S G S F C R N K 3111 K L K Y L A F L H 3 112 L K Y L A F L H K 3 147 D G G S C C P Q G 3148 G G S C C P Q G H 3 149 G S C C P Q G H A 3 159 E A Y K K V C L S 3162 K K V C L S G A P 3 171 H E V G W K Y Q A 3 175 W K Y Q A V T A T 3182 A T L E E K R K E 3 190 E K A E I H Y R K 3 192 A E I H Y R K N K 3215 K K I D K Y T E S 3 218 D K Y T E S P G G 3 219 K Y T E S P G G G 3237 K T I A P L A A T 3 239 I A P L A A T R A 3 240 A P L A A T R A T 3251 G H P G G R T P R 3 254 G G R T P R A G S 3 269 A L S A R A P V P 3278 A A S P A A W L P 3 301 S S T Y D S L S P 3 305 D S L S P Y G P R 3306 S L S P Y G P R N 3 314 N P L P N P R H S 3 325 G G G G L K K P A 3330 K K P A R H C Q G 3 340 K H N V L A R G K 3 352 K P K S E N N S W 3359 S W Y V E N G R P 3 368 A D L A G S G Y C 3 372 G S G Y C G A L W 3374 G Y C G A L W K A 3 381 K A I E S L E E G 3 384 E S L E E G L G G 3389 G L G G K Q K D K 3 391 G G K Q K D K E R 3 4 H T T K T F P L R 2 5T T K T F P L R A 2 15 H I V V E S I R D 2 16 I V V E S I R D H 2 17 V VE S I R D H S 2 19 E S I R D H S G Q 2 32 D K K V D L L V P 2 36 D L L VP T K V T 2 59 F V G S Y K L A Y 2 63 Y K L A Y S N D G 2 64 K L A Y S ND G E 2 66 A Y S N D G E H W 2 89 L G R K A V V V S 2 94 V V V S C E G IN 2 115 L A F L H K R M N 2 122 M N T N P S R R P 2 124 T N P S R R P YH 2 130 P Y H F Q V P S R 2 133 F Q V P S R I F W 2 135 V P S R I F W RQ 2 145 K A D G G S C C P 2 160 A Y K K V C L S G 2 163 K V C L S G A PH 2 167 S G A P H E V G W 2 178 Q A V T A T L E E 2 179 A V T A T L E EK 2 181 T A T L E E K R K 2 189 K E K A E I H Y R 2 191 K A E I H Y R KN 2 198 K N K Q L M R L Q 2 199 N K Q L M R L Q K 2 207 K Q A E K N M KK 2 211 K N M K K K I D K 2 216 K I D K Y T E S P 2 223 S P G G G S P RG 2 232 L G F I F K T I A 2 236 F K T I A P L A A 2 238 T I A P L A A TR 2 243 A A T R A T R I G 2 247 A T R I G H P G G 2 250 I G H P G G R TP 2 252 H P G G R T P R A 2 260 A G S S A H R P P 2 271 S A R A P V P AA 2 281 P A A W L P L R T 2 285 L P L R T P W T R 2 297 C P T S S S T YD 2 298 P T S S S T Y D S 2 302 S T Y D S L S P Y 2 303 T Y D S L S P YG 2 309 P Y G P R N P L P 2 331 K P A R H C Q G Q 2 342 N V L A R G K PQ 2 343 V L A R G K P Q R 2 348 K P Q R K P K S E 2 356 E N N S W Y V EN 2 357 N N S W Y V E N G 2 364 N G R P A D L A G 2 388 E G L G G K Q KD 2 393 K Q K D K E R K A 2 395 K D K E R K A E N 2 396 D K E R K A E NG 2 397 K E R K A E N G P 2 14 L H I V V E S I R 1 20 S I R D H S G Q K1 24 H S G Q K M K Q D 1 41 T K V T G I I T Q 1 43 V T G I I T Q G A 144 T G I I T Q G A K 1 47 I T Q G A K D F G 1 54 F G H V Q F V G S 1 58Q F V G S Y K L A 1 62 S Y K L A Y S N D 1 70 D G E H W T V Y Q 1 73 H WT V Y Q D E K 1 74 W T V Y Q D E K Q 1 76 V Y Q D E K Q R K 1 85 D K V LL G R K A 1 97 S C E G I N I S G 1 102 N I S G S F C R N 1 106 S F C R NK L K Y 1 118 L H K R M N T N P 1 123 N T N P S R R P Y 1 134 Q V P S RI F W R 1 136 P S R I F W R Q E 1 139 I F W R Q E K A D 1 143 Q E K A DG G S C 1 146 A D G G S C C P Q 1 150 S C C P Q G H A S 1 152 C P Q G HA S E A 1 157 A S E A Y K K V C 1 169 A P H E V G W K Y 1 177 Y Q A V TA T L E 1 201 Q L M R L Q K Q A 1 213 M K K K I D K Y T 1 217 I D K Y TE S P G 1 220 Y T E S P G G G S 1 221 T E S P G G G S P 1 244 A T R A TR I G H 1 267 P P A L S A R A P 1 270 L S A R A P V P A 1 275 P V P A AS P A A 1 280 S P A A W L P L R 1 282 A A W L P L R T P 1 284 W L P L RT P W T 1 286 P L R T P W T R P 1 290 P W T R P S S C P 1 291 W T R P SS C P T 1 295 S S C P T S S S T 1 304 Y D S L S P Y G P 1 307 L S P Y GP R N P 1 310 Y G P R N P L P N 1 316 L P N P R H S P S 1 317 P N P R HS P S G 1 323 P S G G G G L K K 1 329 L K K P A R H C Q 1 332 P A R H CQ G Q K 1 337 Q G Q K H N V L A 1 339 Q K H N V L A R G 1 341 H N V L AR G K P 1 344 L A R G K P Q R K 1 355 S E N N S W Y V E 1 360 W Y V E NG R P A 1 361 Y V E N G R P A D 1 363 E N G R P A D L A 1 369 D L A G SG Y C G 1 370 L A G S G Y C G A 1 379 L W K A I E S L E 1 380 W K A I ES L E E 1 383 I E S L E E G L G 1 387 E E G L G G K Q K 1

[0833] TABLE XXXIII SEQ. Pos 1 2 3 4 5 6 7 8 9 score ID NO. 151P3D4 v.1:HLA Peptide Scoring Results B*4402 9-mers SYFPEITHI 42 V E A E Q A K V F24 146 E D D T V V V A L 18 186 A V I A S F D Q L 18 153 A L D L Q G V VF 17 162 P Y F P R L G R Y 17 34 A E N G P H L L V 16 69 A F G S G I H KI 16 159 V V F P Y F P R L 16 230 N T V P G V R N Y 16 284 A Q I A K V GQ I 16 1 M K S L L L L V L 15 62 K F Y R D P T A F 15 121 D A S L V I TD L 15 145 L E D D T V V V A 15 255 S N F N G R F Y Y 15 264 L I H P T KL T Y 15 288 K V G Q I F A A W 15 329 E A A V R F V G F 15 2 K S L L L LV L I 14 10 I S I C W A D H L 14 33 Q A E N G P H L L 14 44 A E Q A K VF S H 14 51 S H R G G N V T L 14 56 N V T L P C K F Y 14 73 G I H K I RI K W 14 90 K E V D V F V S M 14 97 S M G Y H K K T Y 14 180 A C L D Q DA V I 14 183 D Q D A V I A S F 14 190 S F D Q L Y D A W 14 209 W L S D GS V Q Y 14 256 N F N G R F Y Y L 14 278 A C L N D G A Q I 14 291 Q I F AA W K I L 14 293 F A A W K I L G Y 14 336 G F P D K K H K L 14 337 F P DK K H K L Y 14 345 Y G V Y C F R A Y 14 6 L L V L I S I C W 13 22 Y T LD H D R A I 13 55 G N V T L P C K F 13 87 D Y L K E V D V F 13 118 S D SD A S L V I 13 123 S L V I T D L T L 13 126 I T D L T L E D Y 13 131 L ED Y G R Y K C 13 137 Y K C E V I E G L 13 243 K D K S R Y D V F 13 249 DV F C F T S N F 13 262 Y Y L I H P T K L 13 290 G Q I F A A W K I 13 326S P T E A A V R F 13 4 L L L L V L I S I 12 16 D H L S D N Y T L 12 24 LD H D R A I H I 12 76 K I R I K W T K L 12 80 K W T K L T S D Y 12 105 YG G Y Q G R V F 12 106 G G Y Q G R V F L 12 116 G G S D S D A S L 12 142I E G L E D D T V 12 148 D T V V V A L D L 12 155 D L Q G V V F P Y 12164 F P R L G R Y N L 12 166 R L G R Y N L N F 12 175 H E A Q Q A C L D12 194 L Y D A W R G G L 12 196 D A W R G G L D W 12 202 L D W C N A G WL 12 233 P G V R N Y G F W 12 245 K S R Y D V F C F 12 253 F T S N F N GR F 12 254 T S N F N G R F Y 12 273 D E A V Q A C L N 12 300 G Y D R C DA G W 12 308 W L A D G S V R Y 12 310 A D G S V R Y P I 12 328 T E A A VR F V G 12 340 K K H K L Y G V Y 12 342 H K L Y G V Y C F 12 14 W A D HL S D N Y 11 32 I Q A E N G P H L 11 81 W T K L T S D Y L 11 129 L T L ED Y G R Y 11 139 C E V I E G L E D 11 156 L Q G V V F P Y F 11 187 V I AS F D Q L Y 11 201 G L D W C N A G W 11 223 R E P C G G Q N T 11 232 V PG V R N Y G F 11 240 F W D K D K S R Y 11 301 Y D R C D A G W L 11 92 VD V F V S M G Y 10 100 Y H K K T Y G G Y 10 174 F H E A Q Q A C L 10 257F N G R F Y Y L I 10 272 Y D E A V Q A C L 10 285 Q I A K V G Q I F 1071 G S G I H K I R I 9 134 Y G R Y K C E V I 9 211 S D G S V Q Y P I 9287 A K V G Q I F A A 9 35 E N G P H L L V E 8 66 D P T A F G S G I 8 72S G I H K I R I K 8 77 I R I K W T K L T 7 122 A S L V I T D L T 7 189 AS F D Q L Y D A 7 215 V Q Y P I T K P R 7 263 Y L I H P T K L T 7 335 VG F P D K K H K 7 8 V L I S I C W A D 6 25 D H D R A I H I Q 6 74 I H KI R I K W T 6 75 H K I R I K W T K 6 124 L V I T D L T L E 6 132 E D Y GR Y K C E 6 140 E V I E G L E D D 6 217 Y P I T K P R E P 6 316 Y P I SR P R R R 6 318 I S R P R R R C S 6 324 R C S P T E A A V 6 3 S L L L LV L I S 5 15 A D H L S D N Y T 5 27 D R A I H I Q A E 5 64 Y R D P T A FG S 5 70 F G S G I H K I R 5 84 L T S D Y L K E V 5 96 V S M G Y H K K T5 165 P R L G R Y N L N 5 177 A Q Q A C L D Q D 5 182 L D Q D A V I A S5 197 A W R G G L D W C 5 200 G G L D W C N A G 5 214 S V Q Y P I T K P5 224 E P C G G Q N T V 5 275 A V Q A C L N D G 5 280 L N D G A Q I A K5 281 N D G A Q I A K V 5 282 D G A Q I A K V G 5 294 A A W K I L G Y D5 314 V R Y P I S R P R 5 319 S R P R R R C S P 5 330 A A V R F V G F P5 5 L L L V L I S I C 4 7 L V L I S I C W A 4 17 H L S D N Y T L D 4 18L S D N Y T L D H 4 28 R A I H I Q A E N 4 29 A I H I Q A E N G 4 30 I HI Q A E N G P 4 36 N G P H L L V E A 4 37 G P H L L V E A E 4 47 A K V FS H R G G 4 48 K V F S H R G G N 4 52 H R G G N V T L P 4 57 V T L P C KF Y R 4 61 C K F Y R D P T A 4 68 T A F G S G I H K 4 91 E V D V F V S MG 4 107 G Y Q G R V F L K 4 108 Y Q G R V F L K G 4 120 S D A S L V I TD 4 143 E G L E D D T V V 4 144 G L E D D T V V V 4 160 V F P Y F P R LG 4 169 R Y N L N F H E A 4 170 Y N L N F H E A Q 4 172 L N F H E A Q QA 4 207 A G W L S D G S V 4 219 I T K P R E P C G 4 222 P R E P C G G QN 4 231 T V P G V R N Y G 4 259 G R F Y Y L I H P 4 260 R F Y Y L I H PT 4 268 T K L T Y D E A V 4 270 L T Y D E A V Q A 4 271 T Y D E A V Q AC 4 277 Q A C L N D G A Q 4 296 W K I L G Y D R C 4 297 K I L G Y D R CD 4 299 L G Y D R C D A G 4 303 R C D A G W L A D 4 306 A G W L A D G SV 4 309 L A D G S V R Y P 4 313 S V R Y P I S R P 4 317 P I S R P R R RC 4 325 C S P T E A A V R 4 11 S I C W A D H L S 3 26 H D R A I H I Q A3 39 H L L V E A E Q A 3 43 E A E Q A K V F S 3 45 E Q A K V F S H R 350 F S H R G G N V T 3 53 R G G N V T L P C 3 65 R D P T A F G S G 3 82T K L T S D Y L K 3 83 K L T S D Y L K E 3 86 S D Y L K E V D V 3 95 F VS M G Y H K K 3 109 Q G R V F L K G G 3 111 R V F L K G G S D 3 115 K GG S D S D A S 3 117 G S D S D A S L V 3 119 D S D A S L V I T 3 125 V IT D L T L E D 3 138 K C E V I E G L E 3 152 V A L D L Q G V V 3 154 L DL Q G V V F P 3 163 Y F P R L G R Y N 3 167 L G R Y N L N F H 3 173 N FH E A Q Q A C 3 176 E A Q Q A C L D Q 3 179 Q A C L D Q D A V 3 181 C LD Q D A V I A 3 210 L S D G S V Q Y P 3 213 G S V Q Y P I T K 3 220 T KP R E P C G G 3 226 C G G Q N T V P G 3 228 G Q N T V P G V R 3 237 N YG F W D K D K 3 238 Y G F W D K D K S 3 239 G F W D K D K S R 3 244 D KS R Y D V F C 3 246 S R Y D V F C F T 3 251 F C F T S N F N G 3 252 C FT S N F N G R 3 261 F Y Y L I H P T K 3 265 I H P T K L T Y D 3 274 E AV Q A C L N D 3 295 A W K I L G Y D R 3 312 G S V R Y P I S R 3 323 R RC S P T E A A 3 331 A V R F V G F P D 3 332 V R F V G F P D K 3 333 R FV G F P D K K 3 334 F V G F P D K K H 3 341 K H K L Y G V Y C 3 13 C W AD H L S D N 2 19 S D N Y T L D H D 2 20 D N Y T L D H D R 2 21 N Y T L DH D R A 2 23 T L D H D R A I H 2 38 P H L L V E A E Q 2 40 L L V E A E QA K 2 49 V F S H R G G N V 2 58 T L P C K F Y R D 2 63 F Y R D P T A F G2 78 R I K W T K L T S 2 79 I K W T K L T S D 2 85 T S D Y L K E V D 289 L K E V D V F V S 2 93 D V F V S M G Y H 2 102 K K T Y G G Y Q G 2103 K T Y G G Y Q G R 2 127 T D L T L E D Y G 2 130 T L E D Y G R Y K 2136 R Y K C E V I E G 2 147 D D T V V V A L D 2 149 T V V V A L D L Q 2150 V V V A L D L Q G 2 151 V V A L D L Q G V 2 161 F P Y F P R L G R 2171 N L N F H E A Q Q 2 184 Q D A V I A S F D 2 188 I A S F D Q L Y D 2192 D Q L Y D A W R G 2 193 Q L Y D A W R G G 2 195 Y D A W R G G L D 2203 D W C N A G W L S 2 205 C N A G W L S D G 2 208 G W L S D G S V Q 2225 P C G G Q N T V P 2 227 G G Q N T V P G V 2 236 R N Y G F W D K D 2241 W D K D K S R Y D 2 242 D K D K S R Y D V 2 247 R Y D V F C F T S 2258 N G R F Y Y L I H 2 269 K L T Y D E A V Q 2 279 C L N D G A Q I A 2292 I F A A W K I L G 2 302 D R C D A G W L A 2 304 C D A G W L A D G 2307 G W L A D G S V R 2 311 D G S V R Y P I S 2 315 R Y P I S R P R R 2320 R P R R R C S P T 2 321 P R R R C S P T E 2 327 P T E A A V R F V 2343 K L Y G V Y C F R 2 9 L I S I C W A D H 1 12 I C W A D H L S D 1 41L V E A E Q A K V 1 46 Q A K V F S H R G 1 54 G G N V T L P C K 1 59 L PC K F Y R D P 1 60 P C K F Y R D P T 1 88 Y L K E V D V F V 1 99 G Y H KK T Y G G 1 101 H K K T Y G G Y Q 1 104 T Y G G Y Q G R V 1 112 V F L KG G S D S 1 113 F L K G G S D S D 1 114 L K G G S D S D A 1 128 D L T LE D Y G R 1 133 D Y G R Y K C E V 1 135 G R Y K C E V I E 1 141 V I E GL E D D T 1 157 Q G V V F P Y F P 1 168 G R Y N L N F H E 1 191 F D Q LY D A W R 1 198 W R G G L D W C N 1 199 R G G L D W C N A 1 204 W C N AG W L S D 1 206 N A G W L S D G S 1 212 D G S V Q Y P I T 1 216 Q Y P IT K P R E 1 218 P I T K P R E P C 1 221 K P R E P C G G Q 1 229 Q N T VP G V R N 1 234 G V R N Y G F W D 1 235 V R N Y G F W D K 1 248 Y D V FC F T S N 1 250 V F C F T S N F N 1 266 H P T K L T Y D E 1 267 P T K LT Y D E A 1 283 G A Q I A K V G Q 1 286 I A K V G Q I F A 1 289 V G Q IF A A W K 1 298 I L G Y D R C D A 1 305 D A G W L A D G S 1 322 R R R CS P T E A 1 338 P D K K H K L Y G 1 339 D K K H K L Y G V 1 346 G V Y CF R A Y N 1 151P3D4 v.2: HLA Peptide Scoring Results B*4402 9-mersSYFPEITHI 209 A E K N M K K K I 25 362 V E N G R P A D L 23 158 S E A YK K V C L 22 192 A E I H Y R K N K 19 283 A W L P L R T P W 18 99 E G IN I S G S F 17 185 E E K R K E K A E 17 371 A G S G Y C G A L 17 51 A KD F G H V Q F 16 80 E K Q R K D K V L 16 123 N T N P S R R P Y 16 226 GG S P R G L G F 16 378 A L W K A I E S L 16 387 E E G L G G K Q K 16 66A Y S N D G E H W 15 104 S G S F C R N K L 15 106 S F C R N K L K Y 15125 N P S R R P Y H F 15 133 F Q V P S R I F W 15 167 S G A P H E V G W15 189 K E K A E I H Y R 15 212 N M K K K I D K Y 15 234 F I F K T I A PL 15 262 S S A H R P P A L 15 279 A S P A A W L P L 15 400 K A E N G P HL L 15 1 M L E H T T K T F 14 3 E H T T K T F P L 14 6 T K T F P L R A L14 30 K Q D K K V D L L 14 98 C E G I N I S G S 14 107 F C R N K L K Y L14 109 R N K L K Y L A F 14 169 A P H E V G W K Y 14 194 I H Y R K N K QL 14 221 T E S P G G G S P 14 296 S C P T S S S T Y 14 308 S P Y G P R NP L 14 8 T F P L R A L H I 13 18 V E S I R D H S G 13 46 I I T Q G A K DF 13 57 V Q F V G S Y K L 13 59 F V G S Y K L A Y 13 81 K Q R K D K V LL 13 110 N K L K Y L A F L 13 176 K Y Q A V T A T L 13 224 P G G G S P RG L 13 231 G L G F I F K T I 13 276 V P A A S P A A W 13 302 S T Y D S LS P Y 13 355 S E N N S W Y V E 13 382 A I E S L E E G L 13 383 I E S L EE G L G 13 13 A L H I V V E S I 12 29 M K Q D K K V D L 12 69 N D G E HW T V Y 12 71 G E H W T V Y Q D 12 79 D E K Q R K D K V 12 153 P Q G H AS E A Y 12 171 H E V G W K Y Q A 12 184 L E E K R K E K A 12 228 S P R GL G F I F 12 336 C Q G Q K H N V L 12 352 K P K S E N N S W 12 353 P K SE N N S W Y 12 367 P A D L A G S G Y 12 375 Y C G A L W K A I 12 386 L EE G L G G K Q 12 397 K E R K A E N G P 12 2 L E H T T K T F P 11 38 L VP T K V T G I 11 55 G H V Q F V G S Y 11 93 A V V V S C E G I 11 131 Y HF Q V P S R I 11 132 H F Q V P S R I F 11 188 R K E K A E I H Y 11 197 RK N K Q L M R L 11 227 G S P R G L G F I 11 242 L A A T R A T R I 11 277P A A S P A A W L 11 299 T S S S T Y D S L 11 321 H S P S G G G G L 11372 G S G Y C G A L W 11 399 R K A E N G P H L 11 95 V V S C E G I N I10 143 Q E K A D G G S C 10 186 E K R K E K A E I 10 39 V P T K V T G II 9 272 A R A P V P A A S 9 278 A A S P A A W L P 9 7 K T F P L R A L H8 86 K V L L G R K A V 8 240 A P L A A T R A T 8 264 A H R P P A L S A 8314 N P L P N P R H S 8 42 K V T G I I T Q G 7 150 S C C P Q G H A S 7233 G F I F K T I A P 7 237 K T I A P L A A T 7 265 H R P P A L S A R 7269 A L S A R A P V P 7 274 A P V P A A S P A 7 282 A A W L P L R T P 7364 N G R P A D L A G 7 11 L R A L H I V V E 6 19 E S I R D H S G Q 6 41T K V T G I I T Q 6 105 G S F C R N K L K 6 157 A S E A Y K K V C 6 182A T L E E K R K E 6 230 R G L G F I F K T 6 243 A A T R A T R I G 6 324S G G G G L K K P 6 346 R G K P Q R K P K 6 394 Q K D K E R K A E 6 34 KV D L L V P T K 5 36 D L L V P T K V T 5 37 L L V P T K V T G 5 44 T G II T Q G A K 5 45 G I I T Q G A K D 5 52 K D F G H V Q F V 5 113 K Y L AF L H K R 5 116 A F L H K R M N T 5 127 S R R P Y H F Q V 5 134 Q V P SR I F W R 5 137 S R I F W R Q E K 5 139 I F W R Q E K A D 5 193 E I H YR K N K Q 5 199 N K Q L M R L Q K 5 200 K Q L M R L Q K Q 5 201 Q L M RL Q K Q A 5 215 K K I D K Y T E S 5 238 T I A P L A A T R 5 244 A T R AT R I G H 5 245 T R A T R I G H P 5 248 T R I G H P G G R 5 250 I G H PG G R T P 5 253 P G G R T P R A G 5 255 G R T P R A G S S 5 260 A G S SA H R P P 5 267 P P A L S A R A P 5 287 L R T P W T R P S 5 306 S L S PY G P R N 5 309 P Y G P R N P L P 5 310 Y G P R N P L P N 5 312 P R N PL P N P R 5 329 L K K P A R H C Q 5 338 G Q K H N V L A R 5 342 N V L AR G K P Q 5 345 A R G K P Q R K P 5 348 K P Q R K P K S E 5 363 E N G RP A D L A 5 381 K A I E S L E E G 5 388 E G L G G K Q K D 5 9 F P L R AL H I V 4 12 R A L H I V V E S 4 16 I V V E S I R D H 4 27 Q K M K Q D KK V 4 28 K M K Q D K K V D 4 33 K K V D L L V P T 4 35 V D L L V P T K V4 58 Q F V G S Y K L A 4 68 S N D G E H W T V 4 82 Q R K D K V L L G 487 V L L G R K A V V 4 88 L L G R K A V V V 4 96 V S C E G I N I S 4 97S C E G I N I S G 4 102 N I S G S F C R N 4 115 L A F L H K R M N 4 135V P S R I F W R Q 4 138 R I F W R Q E K A 4 146 A D G G S C C P Q 4 156H A S E A Y K K V 4 159 E A Y K K V C L S 4 160 A Y K K V C L S G 4 165C L S G A P H E V 4 172 E V G W K Y Q A V 4 179 A V T A T L E E K 4 208Q A E K N M K K K 4 210 E K N M K K K I D 4 222 E S P G G G S P R 4 235I F K T I A P L A 4 236 F K T I A P L A A 4 263 S A H R P P A L S 4 271S A R A P V P A A 4 284 W L P L R T P W T 4 285 L P L R T P W T R 4 295S S C P T S S S T 4 300 S S S T Y D S L S 4 315 P L P N P R H S P 4 316L P N P R H S P S 4 320 R H S P S G G G G 4 322 S P S G G G G L K 4 330K K P A R H C Q G 4 333 A R H C Q G Q K H 4 361 Y V E N G R P A D 4 368A D L A G S G Y C 4 384 E S L E E G L G G 4 393 K Q K D K E R K A 4 5 TT K T F P L R A 3 14 L H I V V E S I R 3 20 S I R D H S G Q K 3 23 D H SG Q K M K Q 3 24 H S G Q K M K Q D 3 32 D K K V D L L V P 3 50 G A K D FG H V Q 3 72 E H W T V Y Q D E 3 75 T V Y Q D E K Q R 3 77 Y Q D E K Q RK D 3 78 Q D E K Q R K D K 3 83 R K D K V L L G R 3 85 D K V L L G R K A3 89 L G R K A V V V S 3 101 I N I S G S F C R 3 111 K L K Y L A F L H 3112 L K Y L A F L H K 3 117 F L H K R M N T N 3 119 H K R M N T N P S 3120 K R M N T N P S R 3 121 R M N T N P S R R 3 124 T N P S R R P Y H 3128 R R P Y H F Q V P 3 144 E K A D G G S C C 3 145 K A D G G S C C P 3162 K K V C L S G A P 3 174 G W K Y Q A V T A 3 175 W K Y Q A V T A T 3178 Q A V T A T L E E 3 181 T A T L E E K R K 3 183 T L E E K R K E K 3190 E K A E I H Y R K 3 191 K A E I H Y R K N 3 198 K N K Q L M R L Q 3202 L M R L Q K Q A E 3 211 K N M K K K I D K 3 213 M K K K I D K Y T 3216 K I D K Y T E S P 3 229 P R G L G F I F K 3 239 I A P L A A T R A 3243 R A T R I G H P G 3 247 A T R I G H P G G 3 251 G H P G G R T P R 3252 H P G G R T P R A 3 270 L S A R A P V P A 3 275 P V P A A S P A A 3280 S P A A W L P L R 3 289 T P W T R P S S C 3 291 W T R P S S C P T 3304 Y D S L S P Y G P 3 307 L S P Y G P R N P 3 323 P S G G G G L K K 3325 G G G G L K K P A 3 326 G G G L K K P A R 3 340 K H N V L A R G K 3341 H N V L A R G K P 3 347 G K P Q R K P K S 3 350 Q R K P K S E N N 3354 K S E N N S W Y V 3 356 E N N S W Y V E N 3 357 N N S W Y V E N G 3373 S G Y C G A L W K 3 374 G Y C G A L W K A 3 377 G A L W K A I E S 3389 G L G G K Q K D K 3 4 H T T K T F P L R 2 10 P L R A L H I V V 2 17V V E S I R D H S 2 21 I R D H S G Q K M 2 22 R D H S G Q K M K 2 31 Q DK K V D L L V 2 43 V T G I I T Q G A 2 54 F G H V Q F V G S 2 60 V G S YK L A Y S 2 62 S Y K L A Y S N D 2 63 Y K L A Y S N D G 2 67 Y S N D G EH W T 2 70 D G E H W T V Y Q 2 84 K D K V L L G R K 2 90 G R K A V V V SC 2 114 Y L A F L H K R M 2 122 M N T N P S R R P 2 126 P S R R P Y H FQ 2 136 P S R I F W R Q E 2 148 G G S C C P Q G H 2 152 C P Q G H A S EA 2 155 G H A S E A Y K K 2 163 K V C L S G A P H 2 164 V C L S G A P HE 2 168 G A P H E V G W K 2 170 P H E V G W K Y Q 2 177 Y Q A V T A T LE 2 180 V T A T L E E K R 2 187 K R K E K A E I H 2 195 H Y R K N K Q LM 2 196 Y R K N K Q L M R 2 204 R L Q K Q A E K N 2 205 L Q K Q A E K NM 2 207 K Q A E K N M K K 2 214 K K K I D K Y T E 2 219 K Y T E S P G GG 2 223 S P G G G S P R G 2 225 G G G S P R G L G 2 232 L G F I F K T IA 2 241 P L A A T R A T R 2 254 G G R T P R A G S 2 256 R T P R A G S SA 2 257 T P R A G S S A H 2 259 R A G S S A H R P 2 261 G S S A H R P PA 2 268 P A L S A R A P V 2 273 R A P V P A A S P 2 281 P A A W L P L RT 2 288 R T P W T R P S S 2 292 T R P S S C P T S 2 293 R P S S C P T SS 2 294 P S S C P T S S S 2 298 P T S S S T Y D S 2 301 S S T Y D S L SP 2 311 G P R N P L P N P 2 313 R N P L P N P R H 2 317 P N P R H S P SG 2 318 N P R H S P S G G 2 327 G G L K K P A R H 2 328 G L K K P A R HC 2 331 K P A R H C Q G Q 2 334 R H C Q G Q K H N 2 335 H C Q G Q K H NV 2 337 Q G Q K H N V L A 2 339 Q K H N V L A R G 2 343 V L A R G K P QR 2 344 L A R G K P Q R K 2 351 R K P K S E N N S 2 358 N S W Y V E N GR 2 360 W Y V E N G R P A 2 365 G R P A D L A G S 2 366 R P A D L A G SG 2 379 L W K A I E S L E 2 385 S L E E G L G G K 2 391 G G K Q K D K ER 2 395 K D K E R K A E N 2 396 D K E R K A E N G 2 398 E R K A E N G PH 2 15 H I V V E S I R D 1 25 S G Q K M K Q D K 1 26 G Q K M K Q D K K 140 P T K V T G I I T 1 47 I T Q G A K D F G 1 49 Q G A K D F G H V 1 53D F G H V Q F V G 1 61 G S Y K L A Y S N 1 64 K L A Y S N D G E 1 65 L AY S N D G E H 1 74 W T V Y Q D E K Q 1 76 V Y Q D E K Q R K 1 91 R K A VV V S C E 1 92 K A V V V S C E G 1 103 I S G S F C R N K 1 108 C R N K LK Y L A 1 118 L H K R M N T N P 1 129 R P Y H F Q V P S 1 130 P Y H F QV P S R 1 141 W R Q E K A D G G 1 147 D G G S C C P Q G 1 151 C C P Q GH A S E 1 161 Y K K V C L S G A 1 166 L S G A P H E V G 1 173 V G W K YQ A V T 1 203 M R L Q K Q A E K 1 206 Q K Q A E K N M K 1 218 D K Y T ES P G G 1 258 P R A G S S A H R 1 266 R P P A L S A R A 1 286 P L R T PW T R P 1 290 P W T R P S S C P 1 303 T Y D S L S P Y G 1 305 D S L S PY G P R 1 332 P A R H C Q G Q K 1 359 S W Y V E N G R P 1 369 D L A G SG Y C G 1 376 C G A L W K A I E 1 380 W K A I E S L E E 1 390 L G G K QK D K E 1

[0834] TABLE XXXIV SEQ. Pos 1 2 3 4 5 6 7 8 9 score ID NO. 151P3D4 v.1:HLA Peptide Scoring Results B*5101 9-mers SYFPEITHI 66 D P T A F G S G I25 152 V A L D L Q G V V 25 121 D A S L V I T D L 24 134 Y G R Y K C E VI 22 143 E G L E D D T V V 22 224 E P C G G Q N T V 22 4 L L L L V L I SI 18 179 Q A C L D Q D A V 18 33 Q A E N G P H L L 17 106 G G Y Q G R VF L 17 164 F P R L G R Y N L 17 227 G G Q N T V P G V 17 309 L A D G S VR Y P 17 22 Y T L D H D R A I 16 24 L D H D R A I H I 16 68 T A F G S GI H K 16 161 F P Y F P R L G R 16 180 A C L D Q D A V I 16 196 D A W R GG L D W 16 207 A G W L S D G S V 16 217 Y P I T K P R E P 16 16 D H L SD N Y T L 15 88 Y L K E V D V F V 15 118 S D S D A S L V I 15 282 D G AQ I A K V G 15 305 D A G W L A D G S 15 306 A G W L A D G S V 15 316 Y PI S R P R R R 15 326 S P T E A A V R F 15 2 K S L L L L V L I 14 59 L PC K F Y R D P 14 84 L T S D Y L K E V 14 86 S D Y L K E V D V 14 116 G GS D S D A S L 14 148 D T V V V A L D L 14 185 D A V I A S F D Q 14 242 DK D K S R Y D V 14 262 Y Y L I H P T K L 14 284 A Q I A K V G Q I 14 293F A A W K I L G Y 14 337 F P D K K H K L Y 14 339 D K K H K L Y G V 1441 L V E A E Q A K V 13 69 A F G S G I H K I 13 98 M G Y H K K T Y G 13133 D Y G R Y K C E V 13 137 Y K C E V I E G L 13 144 G L E D D T V V V13 188 I A S F D Q L Y D 13 268 T K L T Y D E A V 13 281 N D G A Q I A KV 13 286 I A K V G Q I F A 13 290 G Q I F A A W K I 13 294 A A W K I L GY D 13 299 L G Y D R C D A G 13 1 M K S L L L L V L 12 37 G P H L L V EA E 12 71 G S G I H K I R I 12 87 D Y L K E V D V F 12 104 T Y G G Y Q GR V 12 105 Y G G Y Q G R V F 12 142 I E G L E D D T V 12 146 E D D T V VV A L 12 211 S D G S V Q Y P I 12 221 K P R E P C G G Q 12 232 V P G V RN Y G F 12 278 A C L N D G A Q I 12 310 A D G S V R Y P I 12 327 P T E AA V R F V 12 329 E A A V R F V G F 12 330 A A V R F V G F P 12 32 I Q AE N G P H L 11 43 E A E Q A K V F S 11 46 Q A K V F S H R G 11 51 S H RG G N V T L 11 159 V V F P Y F P R L 11 176 E A Q Q A C L D Q 11 206 N AG W L S D G S 11 238 Y G F W D K D K S 11 257 F N G R F Y Y L I 11 266 HP T K L T Y D E 11 272 Y D E A V Q A C L 11 274 E A V Q A C L N D 11 283G A Q I A K V G Q 11 336 G F P D K K H K L 11 10 I S I C W A D H L 10 14W A D H L S D N Y 10 28 R A I H I Q A E N 10 34 A E N G P H L L V 10 36N G P H L L V E A 10 76 K I R I K W T K L 10 123 S L V I T D L T L 10145 L E D D T V V V A 10 151 V V A L D L Q G V 10 167 L G R Y N L N F H10 200 G G L D W C N A G 10 202 L D W C N A G W L 10 212 D G S V Q Y P IT 10 277 Q A C L N D G A Q 10 311 D G S V R Y P I S 10 320 R P R R R C SP T 10 335 V G F P D K K H K 10 345 Y G V Y C F R A Y 10 20 D N Y T L DH D R 9 49 V F S H R G G N V 9 53 R G G N V T L P C 9 70 F G S G I H K IR 9 72 S G I H K I R I K 9 117 G S D S D A S L V 9 155 D L Q G V V F P Y9 186 A V I A S F D Q L 9 194 L Y D A W R G G L 9 256 N F N G R F Y Y L9 258 N G R F Y Y L I H 9 270 L T Y D E A V Q A 9 291 Q I F A A W K I L9 301 Y D R C D A G W L 9 324 R C S P T E A A V 9 42 V E A E Q A K V F 854 G G N V T L P C K 8 108 Y Q G R V F L K G 8 109 Q G R V F L K G G 8119 D S D A S L V I T 8 147 D D T V V V A L D 8 174 F H E A Q Q A C L 8183 D Q D A V I A S F 8 192 D Q L Y D A W R G 8 246 S R Y D V F C F T 8289 V G Q I F A A W K 8 79 I K W T K L T S D 7 81 W T K L T S D Y L 7 89L K E V D V F V S 7 129 L T L E D Y G R Y 7 154 L D L Q G V V F P 7 157Q G V V F P Y F P 7 226 C G G Q N T V P G 7 228 G Q N T V P G V R 7 236R N Y G F W D K D 7 261 F Y Y L I H P T K 7 265 I H P T K L T Y D 7 328T E A A V R F V G 7 343 K L Y G V Y C F R 7 7 L V L I S I C W A 6 62 K FY R D P T A F 6 93 D V F V S M G Y H 6 96 V S M G Y H K K T 6 115 K G GS D S D A S 6 132 E D Y G R Y K C E 6 135 G R Y K C E V I E 6 168 G R YN L N F H E 6 182 L D Q D A V I A S 6 193 Q L Y D A W R G G 6 199 R G GL D W C N A 6 210 L S D G S V Q Y P 6 215 V Q Y P I T K P R 6 225 P C GG Q N T V P 6 231 T V P G V R N Y G 6 233 P G V R N Y G F W 6 244 D K SR Y D V F C 6 264 L I H P T K L T Y 6 307 G W L A D G S V R 6 314 V R YP I S R P R 6 325 C S P T E A A V R 6 3 S L L L L V L I S 5 5 L L L V LI S I C 5 12 I C W A D H L S D 5 25 D H D R A I H I Q 5 27 D R A I H I QA E 5 35 E N G P H L L V E 5 45 E Q A K V F S H R 5 50 F S H R G G N V T5 58 T L P C K F Y R D 5 82 T K L T S D Y L K 5 90 K E V D V F V S M 5103 K T Y G G Y Q G R 5 120 S D A S L V I T D 5 124 L V I T D L T L E 5156 L Q G V V F P Y F 5 208 G W L S D G S V Q 5 213 G S V Q Y P I T K 5249 D V F C F T S N F 5 251 F C F T S N F N G 5 259 G R F Y Y L I H P 5260 R F Y Y L I H P T 5 271 T Y D E A V Q A C 5 273 D E A V Q A C L N 5297 K I L G Y D R C D 5 302 D R C D A G W L A 5 18 L S D N Y T L D H 438 P H L L V E A E Q 4 40 L L V E A E Q A K 4 44 A E Q A K V F S H 4 52H R G G N V T L P 4 55 G N V T L P C K F 4 64 Y R D P T A F G S 4 73 G IH K I R I K W 4 74 I H K I R I K W T 4 77 I R I K W T K L T 4 78 R I K WT K L T S 4 85 T S D Y L K E V D 4 100 Y H K K T Y G G Y 4 112 V F L K GG S D S 4 114 L K G G S D S D A 4 126 I T D L T L E D Y 4 127 T D L T LE D Y G 4 128 D L T L E D Y G R 4 130 T L E D Y G R Y K 4 131 L E D Y GR Y K C 4 153 A L D L Q G V V F 4 160 V F P Y F P R L G 4 163 Y F P R LG R Y N 4 165 P R L G R Y N L N 4 170 Y N L N F H E A Q 4 172 L N F H EA Q Q A 4 203 D W C N A G W L S 4 214 S V Q Y P I T K P 4 230 N T V P GV R N Y 4 239 G F W D K D K S R 4 248 Y D V F C F T S N 4 280 L N D G AQ I A K 4 292 I F A A W K I L G 4 333 R F V G F P D K K 4 334 F V G F PD K K H 4 340 K K H K L Y G V Y 4 342 H K L Y G V Y C F 4 344 L Y G V YC F R A 4 346 G V Y C F R A Y N 4 6 L L V L I S I C W 3 19 S D N Y T L DH D 3 30 I H I Q A E N G P 3 39 H L L V E A E Q A 3 57 V T L P C K F Y R3 61 C K F Y R D P T A 3 65 R D P T A F G S G 3 83 K L T S D Y L K E 392 V D V F V S M G Y 3 94 V F V S M G Y H K 3 95 F V S M G Y H K K 3 97S M G Y H K K T Y 3 107 G Y Q G R V F L K 3 125 V I T D L T L E D 3 136R Y K C E V I E G 3 140 E V I E G L E D D 3 150 V V V A L D L Q G 3 162P Y F P R L G R Y 3 166 R L G R Y N L N F 3 173 N F H E A Q Q A C 3 189A S F D Q L Y D A 3 216 Q Y P I T K P R E 3 220 T K P R E P C G G 3 240F W D K D K S R Y 3 241 W D K D K S R Y D 3 243 K D K S R Y D V F 3 250V F C F T S N F N 3 253 F T S N F N G R F 3 263 Y L I H P T K L T 3 269K L T Y D E A V Q 3 275 A V Q A C L N D G 3 285 Q I A K V G Q I F 3 308W L A D G S V R Y 3 312 G S V R Y P I S R 3 315 R Y P I S R P R R 3 318I S R P R R R C S 3 322 R R R C S P T E A 3 332 V R F V G F P D K 3 9 LI S I C W A D H 2 13 C W A D H L S D N 2 15 A D H L S D N Y T 2 17 H L SD N Y T L D 2 21 N Y T L D H D R A 2 26 H D R A I H I Q A 2 31 H I Q A EN G P H 2 47 A K V F S H R G G 2 56 N V T L P C K F Y 2 63 F Y R D P T AF G 2 75 H K I R I K W T K 2 91 E V D V F V S M G 2 99 G Y H K K T Y G G2 101 H K K T Y G G Y Q 2 111 R V F L K G G S D 2 113 F L K G G S D S D2 122 A S L V I T D L T 2 141 V I E G L E D D T 2 149 T V V V A L D L Q2 177 A Q Q A C L D Q D 2 181 C L D Q D A V I A 2 191 F D Q L Y D A W R2 195 Y D A W R G G L D 2 197 A W R G G L D W C 2 204 W C N A G W L S D2 205 C N A G W L S D G 2 209 W L S D G S V Q Y 2 219 I T K P R E P C G2 229 Q N T V P G V R N 2 235 V R N Y G F W D K 2 237 N Y G F W D K D K2 245 K S R Y D V F C F 2 247 R Y D V F C F T S 2 252 C F T S N F N G R2 254 T S N F N G R F Y 2 276 V Q A C L N D G A 2 279 C L N D G A Q I A2 287 A K V G Q I F A A 2 298 I L G Y D R C D A 2 303 R C D A G W L A D2 304 C D A G W L A D G 2 313 S V R Y P I S R P 2 317 P I S R P R R R C2 321 P R R R C S P T E 2 331 A V R F V G F P D 2 338 P D K K H K L Y G2 341 K H K L Y G V Y C 2 8 V L I S I C W A D 1 23 T L D H D R A I H 129 A I H I Q A E N G 1 48 K V F S H R G G N 1 60 P C K F Y R D P T 1 80K W T K L T S D Y 1 139 C E V I E G L E D 1 169 R Y N L N F H E A 1 171N L N F H E A Q Q 1 175 H E A Q Q A C L D 1 184 Q D A V I A S F D 1 187V I A S F D Q L Y 1 198 W R G G L D W C N 1 201 G L D W C N A G W 1 218P I T K P R E P C 1 223 R E P C G G Q N T 1 234 G V R N Y G F W D 1 255S N F N G R F Y Y 1 267 P T K L T Y D E A 1 288 K V G Q I F A A W 1 296W K I L G Y D R C 1 319 S R P R R R C S P 1 151P3D4 v.2: HLA PeptideScoring Results B*5101 9-mers SYFPEITHI 242 L A A T R A T R I 26 39 V PT K V T G I I 24 156 H A S E A Y K K V 23 9 F P L R A L H I V 22 308 S PY G P R N P L 22 268 P A L S A R A P V 20 38 L V P T K V T G I 18 159 EA Y K K V C L S 18 285 L P L R T P W T R 18 35 V D L L V P T K V 17 49 QG A K D F G H V 17 131 Y H F Q V P S R I 17 277 P A A S P A A W L 17 400K A E N G P H L L 17 65 L A Y S N D G E H 16 88 L L G R K A V V V 16 169A P H E V G W K Y 16 224 P G G G S P R G L 16 239 I A P L A A T R A 16314 N P L P N P R H S 16 344 L A R G K P Q R K 16 8 T F P L R A L H I 1512 R A L H I V V E S 15 87 V L L G R K A V V 15 89 L G R K A V V V S 15104 S G S F C R N K L 15 129 R P Y H F Q V P S 15 194 I H Y R K N K Q L15 282 A A W L P L R T P 15 377 G A L W K A I E S 15 13 A L H I V V E SI 14 50 G A K D F G H V Q 14 79 D E K Q R K D K V 14 115 L A F L H K R MN 14 208 Q A E K N M K K K 14 209 A E K N M K K K I 14 231 G L G F I F KT I 14 240 A P L A A T R A T 14 276 V P A A S P A A W 14 289 T P W T R PS S C 14 371 A G S G Y C G A L 14 375 Y C G A L W K A I 14 381 K A I E SL E E G 14 10 P L R A L H I V V 13 125 N P S R R P Y H F 13 135 V P S RI F W R Q 13 168 G A P H E V G W K 13 173 V G W K Y Q A V T 13 181 T A TL E E K R K 13 191 K A E I H Y R K N 13 259 R A G S S A H R P 13 266 R PP A L S A R A 13 267 P P A L S A R A P 13 271 S A R A P V P A A 13 281 PA A W L P L R T 13 318 N P R H S P S G G 13 348 K P Q R K P K S E 13 27Q K M K Q D K K V 12 31 Q D K K V D L L V 12 52 K D F G H V Q F V 12 92K A V V V S C E G 12 95 V V S C E G I N I 12 110 N K L K Y L A F L 12152 C P Q G H A S E A 12 178 Q A V T A T L E E 12 223 S P G G G S P R G12 227 G S P R G L G F I 12 230 R G L G F I F K T 12 252 H P G G R T P RA 12 257 T P R A G S S A H 12 273 R A P V P A A S P 12 280 S P A A W L PL R 12 293 R P S S C P T S S 12 297 C P T S S S T Y D 12 316 L P N P R HS P S 12 327 G G L K K P A R H 12 352 K P K S E N N S W 12 366 R P A D LA G S G 12 370 L A G S G Y C G A 12 373 S G Y C G A L W K 12 68 S N D GE H W T V 11 70 D G E H W T V Y Q 11 80 E K Q R K D K V L 11 86 K V L LG R K A V 11 93 A V V V S C E G I 11 145 K A D G G S C C P 11 176 K Y QA V T A T L 11 186 E K R K E K A E I 11 228 S P R G L G F I F 11 234 F IF K T I A P L 11 243 A A T R A T R I G 11 250 I G H P G G R T P 11 263 SA H R P P A L S 11 274 A P V P A A S P A 11 278 A A S P A A W L P 11 310Y G P R N P L P N 11 311 G P R N P L P N P 11 322 S P S G G G G L K 11324 S G G G G L K K P 11 336 C Q G Q K H N V L 11 388 E G L G G K Q K D11 390 L G G K Q K D K E 11 29 M K Q D K K V D L 10 30 K Q D K K V D L L10 36 D L L V P T K V T 10 57 V Q F V G S Y K L 10 107 F C R N K L K Y L10 147 D G G S C C P Q G 10 165 C L S G A P H E V 10 232 L G F I F K T IA 10 246 R A T R I G H P G 10 331 K P A R H C Q G Q 10 332 P A R H C Q GQ K 10 367 P A D L A G S G Y 10 6 T K T F P L R A L 9 32 D K K V D L L VP 9 53 D F G H V Q F V G 9 54 F G H V Q F V G S 9 60 V G S Y K L A Y S 9112 L K Y L A F L H K 9 127 S R R P Y H F Q V 9 172 E V G W K Y Q A V 9197 R K N K Q L M R L 9 218 D K Y T E S P G G 9 253 P G G R T P R A G 9279 A S P A A W L P L 9 335 H C Q G Q K H N V 9 337 Q G Q K H N V L A 9362 V E N G R P A D L 9 378 A L W K A I E S L 9 399 R K A E N G P H L 93 E H T T K T F P L 8 25 S G Q K M K Q D K 8 44 T G I I T Q G A K 8 77 YQ D E K Q R K D 8 81 K Q R K D K V L L 8 154 Q G H A S E A Y K 8 158 S EA Y K K V C L 8 299 T S S S T Y D S L 8 325 G G G G L K K P A 8 354 K SE N N S W Y V 8 364 N G R P A D L A G 8 391 G G K Q K D K E R 8 11 L R AL H I V V E 7 16 I V V E S I R D H 7 23 D H S G Q K M K Q 7 63 Y K L A YS N D G 7 69 N D G E H W T V Y 7 85 D K V L L G R K A 7 148 G G S C C PQ G H 7 167 S G A P H E V G W 7 175 W K Y Q A V T A T 7 182 A T L E E KR K E 7 226 G G S P R G L G F 7 254 G G R T P R A G S 7 260 A G S S A HR P P 7 262 S S A H R P P A L 7 302 S T Y D S L S P Y 7 321 H S P S G GG G L 7 326 G G G L K K P A R 7 346 R G K P Q R K P K 7 37 L L V P T K VT G 6 41 T K V T G I I T Q 6 61 G S Y K L A Y S N 6 75 T V Y Q D E K Q R6 90 G R K A V V V S C 6 99 E G I N I S G S F 6 113 K Y L A F L H K R 6157 A S E A Y K K V C 6 166 L S G A P H E V G 6 207 K Q A E K N M K K 6212 N M K K K I D K Y 6 225 G G G S P R G L G 6 305 D S L S P Y G P R 6359 S W Y V E N G R P 6 369 D L A G S G Y C G 6 376 C G A L W K A I E 6382 A I E S L E E G L 6 396 D K E R K A E N G 6 1 M L E H T T K T F 5 2L E H T T K T F P 5 5 T T K T F P L R A 5 21 I R D H S G Q K M 5 82 Q RK D K V L L G 5 83 R K D K V L L G R 5 96 V S C E G I N I S 5 102 N I SG S F C R N 5 117 F L H K R M N T N 5 118 L H K R M N T N P 5 128 R R PY H F Q V P 5 164 V C L S G A P H E 5 177 Y Q A V T A T L E 5 183 T L EE K R K E K 5 184 L E E K R K E K A 5 200 K Q L M R L Q K Q 5 269 A L SA R A P V P 5 292 T R P S S C P T S 5 296 S C P T S S S T Y 5 307 L S PY G P R N P 5 342 N V L A R G K P Q 5 358 N S W Y V E N G R 5 384 E S LE E G L G G 5 386 L E E G L G G K Q 5 393 K Q K D K E R K A 5 14 L H I VV E S I R 4 28 K M K Q D K K V D 4 34 K V D L L V P T K 4 46 I I T Q G AK D F 4 72 E H W T V Y Q D E 4 91 R K A V V V S C E 4 114 Y L A F L H KR M 4 139 I F W R Q E K A D 4 141 W R Q E K A D G G 4 160 A Y K K V C LS G 4 174 G W K Y Q A V T A 4 180 V T A T L E E K R 4 187 K R K E K A EI H 4 196 Y R K N K Q L M R 4 203 M R L Q K Q A E K 4 204 R L Q K Q A EK N 4 219 K Y T E S P G G G 4 235 I F K T I A P L A 4 238 T I A P L A AT R 4 241 P L A A T R A T R 4 245 T R A T R I G H P 4 270 L S A R A P VP A 4 304 Y D S L S P Y G P 4 323 P S G G G G L K K 4 328 G L K K P A RH C 4 339 Q K H N V L A R G 4 345 A R G K P Q R K P 4 351 R K P K S E NN S 4 355 S E N N S W Y V E 4 357 N N S W Y V E N G 4 374 G Y C G A L WK A 4 4 H T T K T F P L R 3 26 G Q K M K Q D K K 3 33 K K V D L L V P T3 42 K V T G I I T Q G 3 45 G I I T Q G A K D 3 47 I T Q G A K D F G 348 T Q G A K D F G H 3 58 Q F V G S Y K L A 3 59 F V G S Y K L A Y 3 67Y S N D G E H W T 3 71 G E H W T V Y Q D 3 76 V Y Q D E K Q R K 3 97 S CE G I N I S G 3 103 I S G S F C R N K 3 105 G S F C R N K L K 3 106 S FC R N K L K Y 3 116 A F L H K R M N T 3 121 R M N T N P S R R 3 122 M NT N P S R R P 3 123 N T N P S R R P Y 3 133 F Q V P S R I F W 3 138 R IF W R Q E K A 3 155 G H A S E A Y K K 3 161 Y K K V C L S G A 3 179 A VT A T L E E K 3 188 R K E K A E I H Y 3 190 E K A E I H Y R K 3 193 E IH Y R K N K Q 3 199 N K Q L M R L Q K 3 205 L Q K Q A E K N M 3 211 K NM K K K I D K 3 213 M K K K I D K Y T 3 215 K K I D K Y T E S 3 217 I DK Y T E S P G 3 236 F K T I A P L A A 3 244 A T R A T R I G H 3 248 T RI G H P G G R 3 251 G H P G G R T P R 3 258 P R A G S S A H R 3 272 A RA P V P A A S 3 283 A W L P L R T P W 3 286 P L R T P W T R P 3 287 L RT P W T R P S 3 313 R N P L P N P R H 3 338 G Q K H N V L A R 3 347 G KP Q R K P K S 3 353 P K S E N N S W Y 3 360 W Y V E N G R P A 3 365 G RP A D L A G S 3 368 A D L A G S G Y C 3 379 L W K A I E S L E 3 385 S LE E G L G G K 3 389 G L G G K Q K D K 3 15 H I V V E S I R D 2 17 V V ES I R D H S 2 24 H S G Q K M K Q D 2 40 P T K V T G I I T 2 55 G H V Q FV G S Y 2 56 H V Q F V G S Y K 2 64 K L A Y S N D G E 2 74 W T V Y Q D EK Q 2 78 Q D E K Q R K D K 2 84 K D K V L L G R K 2 101 I N I S G S F CR 2 109 R N K L K Y L A F 2 120 K R M N T N P S R 2 124 T N P S R R P YH 2 130 P Y H F Q V P S R 2 134 Q V P S R I F W R 2 146 A D G G S C C PQ 2 185 E E K R K E K A E 2 189 K E K A E I H Y R 2 192 A E I H Y R K NK 2 202 L M R L Q K Q A E 2 206 Q K Q A E K N M K 2 210 E K N M K K K ID 2 214 K K K I D K Y T E 2 216 K I D K Y T E S P 2 220 Y T E S P G G GS 2 222 E S P G G G S P R 2 229 P R G L G F I F K 2 233 G F I F K T I AP 2 237 K T I A P L A A T 2 264 A H R P P A L S A 2 265 H R P P A L S AR 2 275 P V P A A S P A A 2 288 R T P W T R P S S 2 300 S S S T Y D S LS 2 306 S L S P Y G P R N 2 312 P R N P L P N P R 2 329 L K K P A R H CQ 2 330 K K P A R H C Q G 2 333 A R H C Q G Q K H 2 334 R H C Q G Q K HN 2 340 K H N V L A R G K 2 341 H N V L A R G K P 2 361 Y V E N G R P AD 2 383 I E S L E E G L G 2 392 G K Q K D K E R K 2 394 Q K D K E R K AE 2 395 K D K E R K A E N 2 397 K E R K A E N G P 2 398 E R K A E N G PH 2 7 K T F P L R A L H 1 18 V E S I R D H S G 1 20 S I R D H S G Q K 122 R D H S G Q K M K 1 43 V T G I I T Q G A 1 51 A K D F G H V Q F 1 66A Y S N D G E H W 1 73 H W T V Y Q D E K 1 94 V V V S C E G I N 1 98 C EG I N I S G S 1 100 G I N I S G S F C 1 108 C R N K L K Y L A 1 111 K LK Y L A F L H 1 119 H K R M N T N P S 1 132 H F Q V P S R I F 1 136 P SR I F W R Q E 1 140 F W R Q E K A D G 1 142 R Q E K A D G G S 1 143 Q EK A D G G S C 1 144 E K A D G G S C C 1 149 G S C C P Q G H A 1 151 C CP Q G H A S E 1 163 K V C L S G A P H 1 170 P H E V G W K Y Q 1 171 H EV G W K Y Q A 1 195 H Y R K N K Q L M 1 198 K N K Q L M R L Q 1 201 Q LM R L Q K Q A 1 221 T E S P G G G S P 1 249 R I G H P G G R T 1 255 G RT P R A G S S 1 256 R T P R A G S S A 1 261 G S S A H R P P A 1 284 W LP L R T P W T 1 291 W T R P S S C P T 1 295 S S C P T S S S T 1 298 P TS S S T Y D S 1 301 S S T Y D S L S P 1 303 T Y D S L S P Y G 1 309 P YG P R N P L P 1 315 P L P N P R H S P 1 317 P N P R H S P S G 1 320 R HS P S G G G G 1 343 V L A R G K P Q R 1 349 P Q R K P K S E N 1 350 Q RK P K S E N N 1 356 E N N S W Y V E N 1 363 E N G R P A D L A 1 380 W KA I E S L E E 1 387 E E G L G G K Q K 1

[0835] TABLE XXXV SEQ. Pos 1 2 3 4 5 6 7 8 9 0 score ID NO. 151P3D4 v.1:HLA Peptide Scoring Results A1 10-mers SYFPEITHI 91 E V D V F V S M G Y25 263 Y L I H P T K L T Y 24 253 F T S N F N G R F Y 23 96 V S M G Y HK K T Y 21 117 G S D S D A S L V I 21 292 I F A A W K I L G Y 21 254 T SN F N G R F Y Y 20 64 Y R D P T A F G S G 19 119 D S D A S L V I T D 1933 Q A E N G P H L L V 18 186 A V I A S F D Q L Y 18 327 P T E A A V R FV G 18 344 L Y G V Y C F R A Y 18 138 K C E V I E G L E D 17 336 G F P DK K H K L Y 17 337 F P D K K H K L Y G 17 125 V I T D L T L E D Y 16 126I T D L T L E D Y G 16 128 D L T L E D Y G R Y 16 154 L D L Q G V V F PY 16 161 F P Y F P R L G R Y 16 181 C L D Q D A V I A S 16 229 Q N T V PG V R N Y 16 339 D K K H K L Y G V Y 16 13 C W A D H L S D N Y 15 23 T LD H D R A I H I 15 55 G N V T L P C K F Y 15 79 I K W T K L T S D Y 1599 G Y H K K T Y G G Y 15 208 G W L S D G S V Q Y 15 210 L S D G S V Q YP I 15 222 P R E P C G G Q N T 15 239 G F W D K D K S R Y 15 307 G W L AD G S V R Y 15 18 L S D N Y T L D H D 14 25 D H D R A I H I Q A 14 57 VT L P C K F Y R D 14 85 T S D Y L K E V D V 14 130 T L E D Y G R Y K C14 272 Y D E A V Q A C L N 14 89 L K E V D V F V S M 13 144 G L E D D TV V V A 13 146 E D D T V V V A L D 13 153 A L D L Q G V V F P 13 174 F HE A Q Q A C L D 13 194 L Y D A W R G G L D 13 247 R Y D V F C F T S N 13280 L N D G A Q I A K V 13 107 G Y Q G R V F L K G 12 141 V I E G L E DD T V 12 190 S F D Q L Y D A W R 12 309 L A D G S V R Y P I 12 2 K S L LL L V L I S 11 41 L V E A E Q A K V F 11 43 E A E Q A K V F S H 11 67 PT A F G S G I H K 11 122 A S L V I T D L T L 11 145 L E D D T V V V A L11 201 G L D W C N A G W L 11 230 N T V P G V R N Y G 11 240 F W D K D KS R Y D 11 242 D K D K S R Y D V F 11 14 W A D H L S D N Y T 10 131 L ED Y G R Y K C E 10 183 D Q D A V I A S F D 10 219 I T K P R E P C G G 10271 T Y D E A V Q A C L 10 300 G Y D R C D A G W L 10 303 R C D A G W LA D G 10 22 Y T L D H D R A I H 9 34 A E N G P H L L V E 9 72 S G I H KI R I K W 9 195 Y D A W R G G L D W 9 318 I S R P R R R C S P 9 11 S I CW A D H L S D 8 81 W T K L T S D Y L K 8 82 T K L T S D Y L K E 8 148 DT V V V A L D L Q 8 160 V F P Y F P R L G R 8 165 P R L G R Y N L N F 83 S L L L L V L I S I 7 17 H L S D N Y T L D H 7 52 H R G G N V T L P C7 84 L T S D Y L K E V D 7 103 K T Y G G Y Q G R V 7 129 L T L E D Y G RY K 7 159 V V F P Y F P R L G 7 187 V I A S F D Q L Y D 7 245 K S R Y DV F C F T 7 257 F N G R F Y Y L I H 7 270 L T Y D E A V Q A C 7 335 V GF P D K K H K L 7 10 I S I C W A D H L S 6 50 F S H R G G N V T L 6 51 SH R G G N V T L P 6 70 F G S G I H K I R I 6 77 I R I K W T K L T S 6124 L V I T D L T L E D 6 147 D D T V V V A L D L 6 149 T V V V A L D LQ G 6 175 H E A Q Q A C L D Q 6 203 D W C N A G W L S D 6 213 G S V Q YP I T K P 6 267 P T K L T Y D E A V 6 273 D E A V Q A C L N D 6 291 Q IF A A W K I L G 6 302 D R C D A G W L A D 6 314 V R Y P I S R P R R 6 5L L L V L I S I C W 5 88 Y L K E V D V F V S 5 123 S L V I T D L T L E 5135 G R Y K C E V I E G 5 155 D L Q G V V F P Y F 5 162 P Y F P R L G RY N 5 189 A S F D Q L Y D A W 5 215 V Q Y P I T K P R E 5 255 S N F N GR F Y Y L 5 279 C L N D G A Q I A K 5 287 A K V G Q I F A A W 5 301 Y DR C D A G W L A 5 324 R C S P T E A A V R 5 35 E N G P H L L V E A 4 44A E Q A K V F S H R 4 71 G S G I H K I R I K 4 86 S D Y L K E V D V F 4137 Y K C E V I E G L E 4 212 D G S V Q Y P I T K 4 251 F C F T S N F NG R 4 258 N G R F Y Y L I H P 4 262 Y Y L I H P T K L T 4 264 L I H P TK L T Y D 4 285 Q I A K V G Q I F A 4 311 D G S V R Y P I S R 4 312 G SV R Y P I S R P 4 325 C S P T E A A V R F 4 331 A V R F V G F P D K 4 40L L V E A E Q A K V 3 49 V F S H R G G N V T 3 68 T A F G S G I H K I 394 V F V S M G Y H K K 3 95 F V S M G Y H K K T 3 100 Y H K K T Y G G YQ 3 104 T Y G G Y Q G R V F 3 105 Y G G Y Q G R V F L 3 106 G G Y Q G RV F L K 3 113 F L K G G S D S D A 3 152 V A L D L Q G V V F 3 158 G V VF P Y F P R L 3 163 Y F P R L G R Y N L 3 164 F P R L G R Y N L N 3 168G R Y N L N F H E A 3 185 D A V I A S F D Q L 3 202 L D W C N A G W L S3 207 A G W L S D G S V Q 3 217 Y P I T K P R E P C 3 224 E P C G G Q NT V P 3 234 G V R N Y G F W D K 3 235 V R N Y G F W D K D 3 256 N F N GR F Y Y L I 3 261 F Y Y L I H P T K L 3 289 V G Q I F A A W K I 3 306 AG W L A D G S V R 3 316 Y P I S R P R R R C 3 326 S P T E A A V R F V 3328 T E A A V R F V G F 3 332 V R F V G F P D K K 3 333 R F V G F P D KK H 3 345 Y G V Y C F R A Y N 3 1 M K S L L L L V L I 2 8 V L I S I C WA D H 2 15 A D H L S D N Y T L 2 16 D H L S D N Y T L D 2 19 S D N Y T LD H D R 2 32 I Q A E N G P H L L 2 47 A K V F S H R G G N 2 54 G G N V TL P C K F 2 75 H K I R I K W T K L 2 76 K I R I K W T K L T 2 90 K E V DV F V S M G 2 97 S M G Y H K K T Y G 2 108 Y Q G R V F L K G G 2 116 G GS D S D A S L V 2 118 S D S D A S L V I T 2 120 S D A S L V I T D L 2121 D A S L V I T D L T 2 134 Y G R Y K C E V I E 2 151 V V A L D L Q GV V 2 170 Y N L N F H E A Q Q 2 193 Q L Y D A W R G G L 2 197 A W R G GL D W C N 2 209 W L S D G S V Q Y P 2 211 S D G S V Q Y P I T 2 214 S VQ Y P I T K P R 2 231 T V P G V R N Y G F 2 237 N Y G F W D K D K S 2238 Y G F W D K D K S R 2 246 S R Y D V F C F T S 2 248 Y D V F C F T SN F 2 250 V F C F T S N F N G 2 275 A V Q A C L N D G A 2 284 A Q I A KV G Q I F 2 294 A A W K I L G Y D R 2 297 K I L G Y D R C D A 2 308 W LA D G S V R Y P 2 313 S V R Y P I S R P R 2 319 S R P R R R C S P T 2330 A A V R F V G F P D 2 343 K L Y G V Y C F R A 2 4 L L L L V L I S IC 1 6 L L V L I S I C W A 1 29 A I H I Q A E N G P 1 30 I H I Q A E N GP H 1 31 H I Q A E N G P H L 1 36 N G P H L L V E A E 1 39 H L L V E A EQ A K 1 42 V E A E Q A K V F S 1 48 K V F S H R G G N V 1 58 T L P C K FY R D P 1 59 L P C K F Y R D P T 1 63 F Y R D P T A F G S 1 65 R D P T AF G S G I 1 69 A F G S G I H K I R 1 83 K L T S D Y L K E V 1 92 V D V FV S M G Y H 1 93 D V F V S M G Y H K 1 101 H K K T Y G G Y Q G 1 110 G RV F L K G G S D 1 111 R V F L K G G S D S 1 112 V F L K G G S D S D 1114 L K G G S D S D A S 1 132 E D Y G R Y K C E V 1 133 D Y G R Y K C EV I 1 142 I E G L E D D T V V 1 143 E G L E D D T V V V 1 150 V V V A LD L Q G V 1 166 R L G R Y N L N F H 1 167 L G R Y N L N F H E 1 171 N LN F H E A Q Q A 1 177 A Q Q A C L D Q D A 1 179 Q A C L D Q D A V I 1180 A C L D Q D A V I A 1 191 F D Q L Y D A W R G 1 198 W R G G L D W CN A 1 200 G G L D W C N A G W 1 205 C N A G W L S D G S 1 221 K P R E PC G G Q N 1 225 P C G G Q N T V P G 1 226 C G G Q N T V P G V 1 227 G GQ N T V P G V R 1 228 G Q N T V P G V R N 1 232 V P G V R N Y G F W 1233 P G V R N Y G F W D 1 236 R N Y G F W D K D K 1 241 W D K D K S R YD V 1 244 D K S R Y D V F C F 1 252 C F T S N F N G R F 1 268 T K L T YD E A V Q 1 269 K L T Y D E A V Q A 1 276 V Q A C L N D G A Q 1 277 Q AC L N D G A Q I 1 278 A C L N D G A Q I A 1 281 N D G A Q I A K V G 1283 G A Q I A K V G Q I 1 293 F A A W K I L G Y D 1 295 A W K I L G Y DR C 1 298 I L G Y D R C D A G 1 304 C D A G W L A D G S 1 310 A D G S VR Y P I S 1 317 P I S R P R R R C S 1 329 E A A V R F V G F P 1 334 F VG F P D K K H K 1 340 K K H K L Y G V Y C 1 341 K H K L Y G V Y C F 1151P3D4 v.2: HLA Peptide Scoring Results A1 10-mers SYFPEITHI 68 S N D GE H W T V Y 29 105 G S F C R N K L K Y 27 295 S S C P T S S S T Y 25 58Q F V G S Y K L A Y 22 301 S S T Y D S L S P Y 21 187 K R K E K A E I HY 19 220 Y T E S P G G G S P 19 30 K Q D K K V D L L V 18 168 G A P H EV G W K Y 18 54 F G H V Q F V G S Y 17 211 K N M K K K I D K Y 17 7 K TF P L R A L H I 16 122 M N T N P S R R P Y 16 152 C P Q G H A S E A Y 16352 K P K S E N N S W Y 16 366 R P A D L A G S G Y 16 385 S L E E G L GG K Q 16 157 A S E A Y K K V C L 15 354 K S E N N S W Y V E 15 77 Y Q DE K Q R K D K 13 97 S C E G I N I S G S 13 183 T L E E K R K E K A 13382 A I E S L E E G L G 13 4 H T T K T F P L R A 12 34 K V D L L V P T KV 12 51 A K D F G H V Q F V 12 78 Q D E K Q R K D K V 12 208 Q A E K N MK K K I 12 300 S S S T Y D S L S P 12 322 S P S G G G G L K K 12 361 Y VE N G R P A D L 12 386 L E E G L G G K Q K 12 1 M L E H T T K T F P 1117 V V E S I R D H S G 11 21 I R D H S G Q K M K 11 70 D G E H W T V Y QD 11 123 N T N P S R R P Y H 11 142 R Q E K A D G G S C 11 145 K A D G GS C C P Q 11 191 K A E I H Y R K N K 11 278 A A S P A A W L P L 11 40 PT K V T G I I T Q 10 83 R K D K V L L G R K 10 96 V S C E G I N I S G 10111 K L K Y L A F L H K 10 127 S R R P Y H F Q V P 10 170 P H E V G W KY Q A 10 184 L E E K R K E K A E 10 188 R K E K A E I H Y R 10 216 K I DK Y T E S P G 10 228 S P R G L G F I F K 10 291 W T R P S S C P T S 10303 T Y D S L S P Y G P 10 309 P Y G P R N P L P N 10 367 P A D L A G SG Y C 10 372 G S G Y C G A L W K 10 394 Q K D K E R K A E N 10 396 D K ER K A E N G P 10 81 K Q R K D K V L L G 9 177 Y Q A V T A T L E E 8 182A T L E E K R K E K 8 262 S S A H R P P A L S 8 263 S A H R P P A L S A8 280 S P A A W L P L R T 8 302 S T Y D S L S P Y G 8 31 Q D K K V D L LV P 7 43 V T G I I T Q G A K 7 47 I T Q G A K D F G H 7 103 I S G S F CR N K L 7 167 S G A P H E V G W K 7 180 V T A T L E E K R K 7 195 H Y RK N K Q L M R 7 198 K N K Q L M R L Q K 7 225 G G G S P R G L G F 7 244A T R A T R I G H P 7 247 A T R I G H P G G R 7 279 A S P A A W L P L R7 306 S L S P Y G P R N P 7 321 H S P S G G G G L K 7 323 P S G G G G LK K P 7 337 Q G Q K H N V L A R 7 383 I E S L E E G L G G 7 5 T T K T FP L R A L 6 9 F P L R A L H I V V 6 37 L L V P T K V T G I 6 39 V P T KV T G I I T 6 67 Y S N D G E H W T V 6 74 W T V Y Q D E K Q R 6 82 Q R KD K V L L G R 6 94 V V V S C E G I N I 6 108 C R N K L K Y L A F 6 150 SC C P Q G H A S E 6 159 E A Y K K V C L S G 6 235 I F K T I A P L A A 6237 K T I A P L A A T R 6 243 A A T R A T R I G H 6 256 R T P R A G S SA H 6 288 R T P W T R P S S C 6 298 P T S S S T Y D S L 6 299 T S S S TY D S L S 6 308 S P Y G P R N P L P 6 346 R G K P Q R K P K S 6 363 E NG R P A D L A G 6 379 L W K A I E S L E E 6 3 E H T T K T F P L R 5 20 SI R D H S G Q K M 5 104 S G S F C R N K L K 5 132 H F Q V P S R I F W 5133 F Q V P S R I F W R 5 136 P S R I F W R Q E K 5 149 G S C C P Q G HA S 5 158 S E A Y K K V C L S 5 221 T E S P G G G S P R 5 222 E S P G GG S P R G 5 227 G S P R G L G F I F 5 250 I G H P G G R T P R 5 255 G RT P R A G S S A 5 264 A H R P P A L S A R 5 270 L S A R A P V P A A 5272 A R A P V P A A S P 5 274 A P V P A A S P A A 5 283 A W L P L R T PW T 5 287 L R T P W T R P S S 5 305 D S L S P Y G P R N 5 307 L S P Y GP R N P L 5 312 P R N P L P N P R H 5 314 N P L P N P R H S P 5 320 R HS P S G G G G L 5 358 N S W Y V E N G R P 5 371 A G S G Y C G A L W 5 14L H I V V E S I R D 4 19 E S I R D H S G Q K 4 24 H S G Q K M K Q D K 425 S G Q K M K Q D K K 4 61 G S Y K L A Y S N D 4 87 V L L G R K A V V V4 114 Y L A F L H K R M N 4 126 P S R R P Y H F Q V 4 137 S R I F W R QE K A 4 166 L S G A P H E V G W 4 210 E K N M K K K I D K 4 224 P G G GS P R G L G 4 226 G G S P R G L G F I 4 230 R G L G F I F K T I 4 232 LG F I F K T I A P 4 238 T I A P L A A T R A 4 261 G S S A H R P P A L 4265 H R P P A L S A R A 4 294 P S S C P T S S S T 4 316 L P N P R H S PS G 4 329 L K K P A R H C Q G 4 350 Q R K P K S E N N S 4 362 V E N G RP A D L A 4 364 N G R P A D L A G S 4 373 S G Y C G A L W K A 4 376 C GA L W K A I E S 4 378 A L W K A I E S L E 4 384 E S L E E G L G G K 4389 G L G G K Q K D K E 4 6 T K T F P L R A L H 3 29 M K Q D K K V D L L3 44 T G I I T Q G A K D 3 48 T Q G A K D F G H V 3 53 D F G H V Q F V GS 3 57 V Q P V G S Y K L A 3 63 Y K L A Y S N D G E 3 76 V Y Q D E K Q RK D 3 84 K D K V L L G R K A 3 88 L L G R K A V V V S 3 101 I N I S G SF C R N 3 107 F C R N K L K Y L A 3 117 F L H K R M N T N P 3 134 Q V PS R I F W R Q 3 165 C L S G A P H E V G 3 179 A V T A T L E E K R 3 192A E I H Y R K N K Q 3 206 Q K Q A E K N M K K 3 223 S P G G G S P R G L3 234 F I F K T I A P L A 3 324 S G G G G L K K P A 3 332 P A R H C Q GQ K H 3 336 C Q G Q K H N V L A 3 340 K H N V L A R G K P 3 344 L A R GK P Q R K P 3 359 S W Y V E N G R P A 3 10 P L R A L H I V V E 2 13 A LH I V V E S I R 2 22 R D H S G Q K M K Q 2 26 G Q K M K Q D K K V 2 35 VD L L V P T K V T 2 49 Q G A K D F G H V Q 2 52 K D F G H V Q F V G 2 56H V Q F V G S Y K L 2 62 S Y K L A Y S N D G 2 73 H W T V Y Q D E K Q 280 E K Q R K D K V L L 2 106 S F C R N K L K Y L 2 110 N K L K Y L A F LH 2 112 L K Y L A F L H K R 2 131 Y H F Q V P S R I F 2 146 A D G G S CC P Q G 2 154 Q G H A S E A Y K K 2 155 G H A S E A Y K K V 2 161 Y K KV C L S G A P 2 176 K Y Q A V T A T L E 2 181 T A T L E E K R K E 2 190E K A E I H Y R K N 2 194 I H Y R K N K Q L M 2 196 Y R K N K Q L M R L2 197 R K N K Q L M R L Q 2 199 N K Q L M R L Q K Q 2 203 M R L Q K Q AE K N 2 207 K Q A E K N M K K K 2 229 P R G L G F I F K T 2 240 A P L AA T R A T R 2 248 T R I G H P G G R T 2 260 A G S S A H R P P A 2 269 AL S A R A P V P A 2 271 S A R A P V P A A S 2 277 P A A S P A A W L P 2282 A A W L P L R T P W 2 296 S C P T S S S T Y D 2 304 Y D S L S P Y GP R 2 310 Y G P R N P L P N P 2 328 G L K K P A R H C Q 2 335 H C Q G QK H N V L 2 343 V L A R G K P Q R K 2 345 A R G K P Q R K P K 2 355 S EN N S W Y V E N 2 368 A D L A G S G Y C G 2 369 D L A G S G Y C G A 2375 Y C G A L W K A I E 2 387 E E G L G G K Q K D 2 392 G K Q K D K E RK A 2 399 R K A E N G P H L L 2 11 L R A L H I V V E S 1 12 R A L H I VV E S I 1 16 I V V E S I R D H S 1 18 V E S I R D H S G Q 1 23 D H S G QK M K Q D 1 27 Q K M K Q D K K V D 1 33 K K V D L L V P T K 1 36 D L L VP T K V T G 1 42 K V T G I I T Q G A 1 55 G H V Q F V G S Y K 1 59 F V GS Y K L A Y S 1 60 V G S Y K L A Y S N 1 64 K L A Y S N D G E H 1 65 L AY S N D G E H W 1 66 A Y S N D G E H W T 1 79 D E K Q R K D K V L 1 85 DK V L L G R K A V 1 86 K V L L G R K A V V 1 89 L G R K A V V V S C 1 90G R K A V V V S C E 1 93 A V V V S C E G I N 1 95 V V S C E G I N I S 199 E G I N I S G S F C 1 102 N I S G S F C R N K 1 115 L A F L H K R M NT 1 116 A F L H K R M N T N 1 119 H K R M N T N P S R 1 129 R P Y H F QV P S R 1 135 V P S R I F W R Q E 1 140 F W R Q E K A D G G 1 143 Q E KA D G G S C C 1 156 H A S E A Y K K V C 1 160 A Y K K V C L S G A 1 162K K V C L S G A P H 1 164 V C L S G A P H E V 1 169 A P H E V G W K Y Q1 171 H E V G W K Y Q A V 1 172 E V G W K Y Q A V T 1 173 V G W K Y Q AV T A 1 174 G W K Y Q A V T A T 1 193 E I H Y R K N K Q L 1 201 Q L M RL Q K Q A E 1 204 R L Q K Q A E K N M 1 205 L Q K Q A E K N M K 1 209 AE K N M K K K I D 1 219 K Y T E S P G G G S 1 231 G L G F I F K T I A 1236 F K T I A P L A A T 1 241 P L A A T R A T R I 1 245 T R A T R I G HP G 1 249 R I G H P G G R T P 1 251 G H P G G R T P R A 1 252 H P G G RT P R A G 1 253 P G G R T P R A G S 1 258 P R A G S S A H R P 1 267 P PA L S A R A P V 1 268 P A L S A R A P V P 1 276 V P A A S P A A W L 1284 W L P L R T P W T R 1 286 P L R T P W T R P S 1 315 P L P N P R H SP S 1 319 P R H S P S G G G G 1 325 G G G G L K K P A R 1 333 A R H C QG Q K H N 1 341 H N V L A R G K P Q 1 351 R K P K S E N N S W 1 356 E NN S W Y V E N G 1 360 W Y V E N G R P A D 1 374 G Y C G A L W K A I 1388 E G L G G K Q K D K 1 393 K Q K D K E R K A E 1 397 K E R K A E N GP H 1 398 E R K A E N G P H L 1

[0836] TABLE XXXVI SEQ. Pos 1 2 3 4 5 6 7 8 9 0 score ID NO. 151P3D4v.1: HLA Peptide Scoring Results A*0201 10-mers SYFPEITHI 3 S L L L L VL I S I 28 40 L L V E A E Q A K V 28 83 K L T S D Y L K E V 25 193 Q L YD A W R G G L 23 68 T A F G S G I H K I 22 141 V I E G L E D D T V 22280 L N D G A Q I A K V 22 144 G L E D D T V V V A 21 201 G L D W C N AG W L 21 6 L L V L I S I C W A 20 9 L I S I C W A D H L 20 145 L E D D TV V V A L 20 150 V V V A L D L Q G V 20 31 H I Q A E N G P H L 19 4 L LL L V L I S I C 18 23 T L D H D R A I H I 18 103 K T Y G G Y Q G R V 18120 S D A S L V I T D L 18 153 A L D L Q G V V F P 18 343 K L Y G V Y CF R A 18 32 I Q A E N G P H L L 17 88 Y L K E V D V F V S 17 122 A S L VI T D L T L 17 151 V V A L D L Q G V V 17 263 Y L I H P T K L T Y 17 283G A Q I A K V G Q I 17 297 K I L G Y D R C D A 17 308 W L A D G S V R YP 17 309 L A D G S V R Y P I 17 326 S P T E A A V R F V 17 335 V G F P DK K H K L 17 48 K V F S H R G G N V 16 73 G I H K I R I K W T 16 113 F LK G G S D S D A 16 123 S L V I T D L T L E 16 206 N A G W L S D G S V 16226 C G G Q N T V P G V 16 264 L I H P T K L T Y D 16 8 V L I S I C W AD H 15 15 A D H L S D N Y T L 15 50 F S H R G G N V T L 15 115 K G G S DS D A S L 15 158 G V V F P Y F P R L 15 166 R L G R Y N L N F H 15 181 CL D Q D A V I A S 15 209 W L S D G S V Q Y P 15 269 K L T Y D E A V Q A15 305 D A G W L A D G S V 15 1 M K S L L L L V L I 14 5 L L L V L I S IC W 14 33 Q A E N G P H L L V 14 75 H K I R I K W T K L 14 136 R Y K C EV I E G L 14 171 N L N F H E A Q Q A 14 173 N F H E A Q Q A C L 14 179 QA C L D Q D A V I 14 188 I A S F D Q L Y D A 14 255 S N F N G R F Y Y L14 261 F Y Y L I H P T K L 14 271 T Y D E A V Q A C L 14 277 Q A C L N DG A Q I 14 285 Q I A K V G Q I F A 14 286 I A K V G Q I F A A 14 11 S IC W A D H L S D 13 39 H L L V E A E Q A K 13 78 R I K W T K L T S D 1387 D Y L K E V D V F V 13 105 Y G G Y Q G R V F L 13 118 S D S D A S L VI T 13 125 V I T D L T L E D Y 13 130 T L E D Y G R Y K C 13 143 E G L ED D T V V V 13 163 Y F P R L G R Y N L 13 178 Q Q A C L D Q D A V 13 185D A V I A S F D Q L 13 210 L S D G S V Q Y P I 13 223 R E P C G G Q N TV 13 270 L T Y D E A V Q A C 13 279 C L N D G A Q I A K 13 323 R R C S PT E A A V 13 17 H L S D N Y T L D H 12 29 A I H I Q A E N G P 12 76 K IR I K W T K L T 12 116 G G S D S D A S L V 12 132 E D Y G R Y K C E V 12142 I E G L E D D T V V 12 155 D L Q G V V F P Y F 12 187 V I A S F D QL Y D 12 256 N F N G R F Y Y L I 12 298 I L G Y D R C D A G 12 338 P D KK H K L Y G V 12 22 Y T L D H D R A I H 11 35 E N G P H L L V E A 11 70F G S G I H K I R I 11 85 T S D Y L K E V D V 11 124 L V I T D L T L E D11 180 A C L D Q D A V I A 11 182 L D Q D A V I A S F 11 241 W D K D K SR Y D V 11 267 P T K L T Y D E A V 11 275 A V Q A C L N D G A 11 289 V GQ I F A A W K I 11 290 G Q I F A A W K I L 11 293 F A A W K I L G Y D 11300 G Y D R C D A G W L 11 34 A E N G P H L L V E 10 57 V T L P C K F YR D 10 58 T L P C K F Y R D P 10 80 K W T K L T S D Y L 10 95 F V S M GY H K K T 10 117 G S D S D A S L V I 10 129 L T L E D Y G R Y K 10 152 VA L D L Q G V V F 10 259 G R F Y Y L I H P T 10 292 I F A A W K I L G Y10 7 L V L I S I C W A D 9 14 W A D H L S D N Y T 9 65 R D P T A F G S GI 9 89 L K E V D V F V S M 9 97 S M G Y H K K T Y G 9 140 E V I E G L ED D T 9 147 D D T V V V A L D L 9 168 G R Y N L N F H E A 9 291 Q I F AA W K I L G 9 2 K S L L L L V L I S 8 21 N Y T L D H D R A I 8 24 L D HD R A I H I Q 8 51 S H R G G N V T L P 8 128 D L T L E D Y G R Y 8 135 GR Y K C E V I E G 8 154 L D L Q G V V F P Y 8 159 V V F P Y F P R L G 8186 A V I A S F D Q L Y 8 196 D A W R G G L D W C 8 219 I T K P R E P CG G 8 231 T V P G V R N Y G F 8 278 A C L N D G A Q I A 8 294 A A W K IL G Y D R 8 12 I C W A D H L S D N 7 42 V E A E Q A K V F S 7 77 I R I KW T K L T S 7 84 L T S D Y L K E V D 7 86 S D Y L K E V D V F 7 121 D AS L V I T D L T 7 133 D Y G R Y K C E V I 7 148 D T V V V A L D L Q 7200 G G L D W C N A G W 7 211 S D G S V Q Y P I T 7 213 G S V Q Y P I TK P 7 230 N T V P G V R N Y G 7 262 Y Y L I H P T K L T 7 287 A K V G QI F A A W 7 288 K V G Q I F A A W K 7 299 L G Y D R C D A G W 7 329 E AA V R F V G F P 7 18 L S D N Y T L D H D 6 28 R A I H I Q A E N G 6 43 EA E Q A K V F S H 6 49 V F S H R G G N V T 6 59 L P C K F Y R D P T 6 64Y R D P T A F G S G 6 72 S G I H K I R I K W 6 90 K E V D V F V S M G 6106 G G Y Q G R V F L K 6 107 G Y Q G R V F L K G 6 108 Y Q G R V F L KG G 6 126 I T D L T L E D Y G 6 170 Y N L N F H E A Q Q 6 177 A Q Q A CL D Q D A 6 198 W R G G L D W C N A 6 246 S R Y D V F C F T S 6 274 E AV Q A C L N D G 6 301 Y D R C D A G W L A 6 303 R C D A G W L A D G 6318 I S R P R R R C S P 6 319 S R P R R R C S P T 6 330 A A V R F V G FP D 6 331 A V R F V G F P D K 6 10 I S I C W A D H L S 5 26 H D R A I HI Q A E 5 27 D R A I H I Q A E N 5 36 N G P H L L V E A E 5 37 G P H L LV E A E Q 5 53 R G G N V T L P C K 5 71 G S G I H K I R I K 5 82 T K L TS D Y L K E 5 93 D V F V S M G Y H K 5 96 V S M G Y H K K T Y 5 111 R VF L K G G S D S 5 112 V F L K G G S D S D 5 114 L K G G S D S D A S 5119 D S D A S L V I T D 5 149 T V V V A L D L Q G 5 161 F P Y F P R L GR Y 5 176 E A Q Q A C L D Q D 5 189 A S F D Q L Y D A W 5 195 Y D A W RG G L D W 5 204 W C N A G W L S D G 5 205 C N A G W L S D G S 5 208 G WL S D G S V Q Y 5 215 V Q Y P I T K P R E 5 218 P I T K P R E P C G 5234 G V R N Y G F W D K 5 249 D V F C F T S N F N 5 253 F T S N F N G RF Y 5 266 H P T K L T Y D E A 5 304 C D A G W L A D G S 5 307 G W L A DG S V R Y 5 312 G S V R Y P I S R P 5 313 S V R Y P I S R P R 5 314 V RY P I S R P R R 5 317 P I S R P R R R C S 5 322 R R R C S P T E A A 5328 T E A A V R F V G F 5 341 K H K L Y G V Y C F 5 20 D N Y T L D H D RA 4 30 I H I Q A E N G P H 4 41 L V E A E Q A K V F 4 46 Q A K V F S H RG G 4 54 G G N V T L P C K F 4 62 K F Y R D P T A F G 4 81 W T K L T S DY L K 4 94 V F V S M G Y H K K 4 127 T D L T L E D Y G R 4 137 Y K C E VI E G L E 4 139 C E V I E G L E D D 4 172 L N F H E A Q Q A C 4 190 S FD Q L Y D A W R 4 197 A W R G G L D W C N 4 214 S V Q Y P I T K P R 4217 Y P I T K P R E P C 4 228 G Q N T V P G V R N 4 238 Y G F W D K D KS R 4 245 K S R Y D V F C F T 4 251 F C F T S N F N G R 4 268 T K L T YD E A V Q 4 276 V Q A C L N D G A Q 4 282 D G A Q I A K V G Q 4 284 A QI A K V G Q I F 4 316 Y P I S R P R R R C 4 324 R C S P T E A A V R 4332 V R F V G F P D K K 4 13 C W A D H L S D N Y 3 19 S D N Y T L D H DR 3 25 D H D R A I H I Q A 3 38 P H L L V E A E Q A 3 52 H R G G N V T LP C 3 56 N V T L P C K F Y R 3 63 F Y R D P T A F G S 3 74 I H K I R I KW T K 3 79 I K W T K L T S D Y 3 98 M G Y H K K T Y G G 3 134 Y G R Y KC E V I E 3 138 K C E V I E G L E D 3 146 E D D T V V V A L D 3 156 L QG V V F P Y F P 3 175 H E A Q Q A C L D Q 3 202 L D W C N A G W L S 3207 A G W L S D G S V Q 3 221 K P R E P C G G Q N 3 229 Q N T V P G V RN Y 3 235 V R N Y G F W D K D 3 239 G F W D K D K S R Y 3 244 D K S R YD V F C F 3 258 N G R F Y Y L I H P 3 260 R F Y Y L I H P T K 3 265 I HP T K L T Y D E 3 306 A G W L A D G S V R 3 310 A D G S V R Y P I S 3320 R P R R R C S P T E 3 321 P R R R C S P T E A 3 333 R F V G F P D KK H 3 334 F V G F P D K K H K 3 340 K K H K L Y G V Y C 3 344 L Y G V YC F R A Y 3 345 Y G V Y C F R A Y N 3 44 A E Q A K V F S H R 2 47 A K VF S H R G G N 2 60 P C K F Y R D P T A 2 67 P T A F G S G I H K 2 91 E VD V F V S M G Y 2 99 G Y H K K T Y G G Y 2 104 T Y G G Y Q G R V F 2 110G R V F L K G G S D 2 160 V F P Y F P R L G R 2 164 F P R L G R Y N L N2 165 P R L G R Y N L N F 2 169 R Y N L N F H E A Q 2 184 Q D A V I A SF D Q 2 194 L Y D A W R G G L D 2 199 R G G L D W C N A G 2 203 D W C NA G W L S D 2 216 Q Y P I T K P R E P 2 222 P R E P C G G Q N T 2 236 RN Y G F W D K D K 2 243 K D K S R Y D V F C 2 247 R Y D V F C F T S N 2257 F N G R F Y Y L I H 2 273 D E A V Q A C L N D 2 296 W K I L G Y D RC D 2 302 D R C D A G W L A D 2 325 C S P T E A A V R F 2 337 F P D K KH K L Y G 2 16 D H L S D N Y T L D 1 61 C K F Y R D P T A F 1 69 A F G SG I H K I R 1 100 Y H K K T Y G G Y Q 1 109 Q G R V F L K G G S 1 167 LG R Y N L N F H E 1 191 F D Q L Y D A W R G 1 192 D Q L Y D A W R G G 1212 D G S V Q Y P I T K 1 220 T K P R E P C G G Q 1 225 P C G G Q N T VP G 1 227 G G Q N T V P G V R 1 232 V P G V R N Y G F W 1 237 N Y G F WD K D K S 1 240 F W D K D K S R Y D 1 248 Y D V F C F T S N F 1 272 Y DE A V Q A C L N 1 295 A W K I L G Y D R C 1 311 D G S V R Y P I S R 1336 G F P D K K H K L Y 1 342 H K L Y G V Y C F R 1 183 D Q D A V I A SF D −1 224 E P C G G Q N T V P −1 242 D K D K S R Y D V F −1 252 C F T SN F N G R F −1 281 N D G A Q I A K V G −1 66 D P T A F G S G I H −2 339D K K H K L Y G V Y −2 233 P G V R N Y G F W D −3 151P3D4 v.2: HLAPeptide Scoring Results A*0201 10-mers SYFPEITHI 37 L L V P T K V T G I27 87 V L L G R K A V V V 27 377 G A L W K A I E S L 23 12 R A L H I V VE S I 20 28 K M K Q D K K V D L 20 381 K A I E S L E E G L 20 86 K V L LG R K A V V 19 278 A A S P A A W L P L 19 5 T T K T F P L R A L 18 88 LL G R K A V V V S 18 233 G F I F K T I A P L 18 269 A L S A R A P V P A18 369 D L A G S G Y C G A 18 7 K T F P L R A L H I 17 20 S I R D H S GQ K M 17 34 K V D L L V P T K V 17 183 T L E E K R K E K A 17 241 P L AA T R A T R I 17 361 Y V E N G R P A D L 17 370 L A G S G Y C G A L 1756 H V Q F V G S Y K L 16 67 Y S N D G E H W T V 16 164 V C L S G A P HE V 16 238 T I A P L A A T R A 16 8 T F P L R A L H I V 15 29 M K Q D KK V D L L 15 36 D L L V P T K V T G 15 51 A K D F G H V Q F V 15 103 I SG S F C R N K L 15 106 S F C R N K L K Y L 15 109 R N K L K Y L A F L 15175 W K Y Q A V T A T L 15 196 Y R K N K Q L M R L 15 223 S P G G G S PR G L 15 226 G G S P R G L G F I 15 234 F I F K T I A P L A 15 276 V P AA S P A A W L 15 385 S L E E G L G G K Q 15 389 G L G G K Q K D K E 15399 R K A E N G P H L L 15 38 L V P T K V T G I I 14 64 K L A Y S N D GE H 14 92 K A V V V S C E G I 14 155 G H A S E A Y K K V 14 202 L M R LQ K Q A E K 14 231 G L G F I F K T I A 14 270 L S A R A P V P A A 14 306S L S P Y G P R N P 14 9 F P L R A L H I V V 13 10 P L R A L H I V V E13 94 V V V S C E G I N I 13 114 Y L A F L H K R M N 13 157 A S E A Y KK V C L 13 171 H E V G W K Y Q A V 13 193 E I H Y R K N K Q L 13 204 R LQ K Q A E K N M 13 230 R G L G F I F K T I 13 261 G S S A H R P P A L 13263 S A H R P P A L S A 13 298 P T S S S T Y D S L 13 320 R H S P S G GG G L 13 335 H C Q G Q K H N V L 13 343 V L A R G K P Q R K 13 373 S G YC G A L W K A 13 378 A L W K A I E S L E 13 2 L E H T T K T F P L 12 11L R A L H I V V E S 12 13 A L H I V V E S I R 12 15 H I V V E S I R D H12 30 K Q D K K V D L L V 12 165 C L S G A P H E V G 12 201 Q L M R L QK Q A E 12 208 Q A E K N M K K K I 12 284 W L P L R T P W T R 12 307 L SP Y G P R N P L 12 26 G Q K M K Q D K K V 11 42 K V T G I I T Q G A 1159 F V G S Y K L A Y S 11 78 Q D E K Q R K D K V 11 115 L A F L H K R MN T 11 117 F L H K R M N T N P 11 182 A T L E E K R K E K 11 236 F K T IA P L A A T 11 237 K T I A P L A A T R 11 239 I A P L A A T R A T 11 267P P A L S A R A P V 11 283 A W L P L R T P W T 11 328 G L K K P A R H CQ 11 334 R H C Q G Q K H N V 11 374 G Y C G A L W K A I 11 45 G I I T QG A K D F 10 48 T Q G A K D F G H V 10 89 L G R K A V V V S C 10 95 V VS C E G I N I S 10 100 G I N I S G S F C R 10 102 N I S G S F C R N K 10111 K L K Y L A F L H K 10 112 L K Y L A F L H K R 10 160 A Y K K V C LS G A 10 167 S G A P H E V G W K 10 173 V G W K Y Q A V T A 10 178 Q A VT A T L E E K 10 212 N M K K K I D K Y T 10 244 A T R A T R I G H P 10249 R I G H P G G R T P 10 272 A R A P V P A A S P 10 274 A P V P A A SP A A 10 344 L A R G K P Q R K P 10 1 M L E H T T K T F P 9 33 K K V D LL V P T K 9 46 I I T Q G A K D F G 9 47 I T Q G A K D F G H 9 80 E K Q RK D K V L L 9 85 D K V L L G R K A V 9 121 R M N T N P S R R P 9 137 S RI F W R Q E K A 9 138 R I F W R Q E K A D 9 216 K I D K Y T E S P G 9264 A H R P P A L S A R 9 271 S A R A P V P A A S 9 280 S P A A W L P LR T 9 281 P A A W L P L R T P 9 291 W T R P S S C P T S 9 302 S T Y D SL S P Y G 9 353 P K S E N N S W Y V 9 364 N G R P A D L A G S 9 382 A IE S L E E G L G 9 4 H T T K T F P L R A 8 16 I V V E S I R D H S 8 32 DK K V D L L V P T 8 97 S C E G I N I S G S 8 123 N T N P S R R P Y H 8129 R P Y H F Q V P S R 8 150 S C C P Q G H A S E 8 174 G W K Y Q A V TA T 8 185 E E K R K E K A E I 8 211 K N M K K K I D K Y 8 240 A P L A AT R A T R 8 242 L A A T R A T R I G 8 248 T R I G H P G G R T 8 251 G HP G G R T P R A 8 255 G R T P R A G S S A 8 265 H R P P A L S A R A 8273 R A P V P A A S P A 8 316 L P N P R H S P S G 8 362 V E N G R P A DL A 8 380 W K A I E S L E E G 8 17 V V E S I R D H S G 7 50 G A K D F GH V Q F 7 54 F G H V Q F V G S Y 7 65 L A Y S N D G E H W 7 66 A Y S N DG E H W T 7 79 D E K Q R K D K V L 7 116 A F L H K R M N T N 7 126 P S RR P Y H F Q V 7 133 F Q V P S R I F W R 7 145 K A D G G S C C P Q 7 158S E A Y K K V C L S 7 168 G A P H E V G W K Y 7 172 E V G W K Y Q A V T7 177 Y Q A V T A T L E E 7 179 A V T A T L E E K R 7 192 A E I H Y R KN K Q 7 194 I H Y R K N K Q L M 7 220 Y T E S P G G G S P 7 229 P R G LG F I F K T 7 235 I F K T I A P L A A 7 247 A T R I G H P G G R 7 260 AG S S A H R P P A 7 279 A S P A A W L P L R 7 282 A A W L P L R T P W 7286 P L R T P W T R P S 7 310 Y G P R N P L P N P 7 314 N P L P N P R HS P 7 315 P L P N P R H S P S 7 322 S P S G G G G L K K 7 324 S G G G GL K K P A 7 342 N V L A R G K P Q R 7 355 S E N N S W Y V E N 7 359 S WY V E N G R P A 7 392 G K Q K D K E R K A 7 398 E R K A E N G P H L 7 35V D L L V P T K V T 6 40 P T K V T G I I T Q 6 43 V T G I I T Q G A K 644 T G I I T Q G A K D 6 81 K Q R K D K V L L G 6 82 Q R K D K V L L G R6 84 K D K V L L G R K A 6 93 A V V V S C E G I N 6 107 F C R N K L K YL A 6 113 K Y L A F L H K R M 6 151 C C P Q G H A S E A 6 163 K V C L SG A P H E 6 180 V T A T L E E K R K 6 199 N K Q L M R L Q K Q 6 200 K QL M R L Q K Q A 6 207 K Q A E K N M K K K 6 215 K K I D K Y T E S P 6243 A A T R A T R I G H 6 262 S S A H R P P A L S 6 287 L R T P W T R PS S 6 288 R T P W T R P S S C 6 295 S S C P T S S S T Y 6 308 S P Y G PR N P L P 6 336 C Q G Q K H N V L A 6 337 Q G Q K H N V L A R 6 338 G QK H N V L A R G 6 371 A G S G Y C G A L W 6 384 E S L E E G L G G K 6 57V Q F V G S Y K L A 5 63 Y K L A Y S N D G E 5 75 T V Y Q D E K Q R K 596 V S C E G I N I S G 5 105 G S F C R N K L K Y 5 139 I F W R Q E K A DG 5 146 A D G G S C C P Q G 5 148 G G S C C P Q G H A 5 156 H A S E A YK K V C 5 159 E A Y K K V C L S G 5 166 L S G A P H E V G W 5 181 T A TL E E K R K E 5 246 R A T R I G H P G G 5 256 R T P R A G S S A H 5 300S S S T Y D S L S P 5 325 G G G G L K K P A R 5 368 A D L A G S G Y C G5 14 L H I V V E S I R D 4 25 S G Q K M K Q D K K 4 31 Q D K K V D L L VP 4 39 V P T K V T G I I T 4 41 T K V T G I I T Q G 4 52 K D F G H V Q FV G 4 58 Q F V G S Y K L A Y 4 68 S N D G E H W T V Y 4 69 N D G E H W TV Y Q 4 76 V Y Q D E K Q R K D 4 83 R K D K V L L G R K 4 90 G R K A V VV S C E 4 91 R K A V V V S C E G 4 101 I N I S G S F C R N 4 127 S R R PY H F Q V P 4 130 P Y H F Q V P S R I 4 134 Q V P S R I F W R Q 4 188 RK E K A E I H Y R 4 203 M R L Q K Q A E K N 4 228 S P R G L G F I F K 4232 L G F I F K T I A P 4 250 I G H P G G R T P R 4 259 R A G S S A H RP P 4 268 P A L S A R A P V P 4 275 P V P A A S P A A W 4 285 L P L R TP W T R P 4 301 S S T Y D S L S P Y 4 323 P S G G G G L K K P 4 340 K HN V L A R G K P 4 346 R G K P Q R K P K S 4 360 W Y V E N G R P A D 4366 R P A D L A G S G Y 4 375 Y C G A L W K A I E 4 376 C G A L W K A IE S 4 379 L W K A I E S L E E 4 383 I E S L E E G L G G 4 394 Q K D K ER K A E N 4 49 Q G A K D F G H V Q 3 60 V G S Y K L A Y S N 3 70 D G E HW T V Y Q D 3 77 Y Q D E K Q R K D K 3 108 C R N K L K Y L A F 3 119 H KR M N T N P S R 3 131 Y H F Q V P S R I F 3 141 W R Q E K A D G G S 3149 G S C C P Q G H A S 3 152 C P Q G H A S E A Y 3 154 Q G H A S E A YK K 3 162 K K V C L S G A P H 3 169 A P H E V G W K Y Q 3 190 E K A E IH Y R K N 3 191 K A E I H Y R K N K 3 219 K Y T E S P G G G S 3 225 G GG S P R G L G F 3 245 T R A T R I G H P G 3 252 H P G G R T P R A G 3254 G G R T P R A G S S 3 277 P A A S P A A W L P 3 294 P S S C P T S SS T 3 326 G G G L K K P A R H 3 327 G G L K K P A R H C 3 329 L K K P AR H C Q G 3 331 K P A R H C Q G Q K 3 332 P A R H C Q G Q K H 3 348 K PQ R K P K S E N 3 351 R K P K S E N N S W 3 365 G R P A D L A G S G 3390 L G G K Q K D K E R 3 18 V E S I R D H S G Q 2 22 R D H S G Q K M KQ 2 53 D F G H V Q F V G S 2 61 G S Y K L A Y S N D 2 62 S Y K L A Y S ND G 2 74 W T V Y Q D E K Q R 2 98 C E G I N I S G S F 2 110 N K L K Y LA F L H 2 118 L H K R M N T N P S 2 120 K R M N T N P S R R 2 140 F W RQ E K A D G G 2 161 Y K K V C L S G A P 2 187 K R K E K A E I H Y 2 205L Q K Q A E K N M K 2 206 Q K Q A E K N M K K 2 213 M K K K I D K Y T E2 214 K K K I D K Y T E S 2 217 I D K Y T E S P G G 2 221 T E S P G G GS P R 2 257 T P R A G S S A H R 2 258 P R A G S S A H R P 2 292 T R P SS C P T S S 2 293 R P S S C P T S S S 2 296 S C P T S S S T Y D 2 303 TY D S L S P Y G P 2 304 Y D S L S P Y G P R 2 305 D S L S P Y G P R N 2311 G P R N P L P N P R 2 330 K K P A R H C Q G Q 2 347 G K P Q R K P KS E 2 350 Q R K P K S E N N S 2 356 E N N S W Y V E N G 2 357 N N S W YV E N G R 2 386 L E E G L G G K Q K 2 395 K D K E R K A E N G 2 21 I R DH S G Q K M K 1 55 G H V Q F V G S Y K 1 71 G E H W T V Y Q D E 1 73 H WT V Y Q D E K Q 1 124 T N P S R R P Y H F 1 125 N P S R R P Y H F Q 1128 R R P Y H F Q V P S 1 135 V P S R I F W R Q E 1 142 R Q E K A D G GS C 1 170 P H E V G W K Y Q A 1 176 K Y Q A V T A T L E 1 184 L E E K RK E K A E 1 189 K E K A E I H Y R K 1 195 H Y R K N K Q L M R 1 197 R KN K Q L M R L Q 1 198 K N K Q L M R L Q K 1 218 D K Y T E S P G G G 1227 G S P R G L G F I F 1 266 R P P A L S A R A P 1 289 T P W T R P S SC P 1 312 P R N P L P N P R H 1 318 N P R H S P S G G G 1 333 A R H C QG Q K H N 1 339 Q K H N V L A R G K 1 345 A R G K P Q R K P K 1 354 K SE N N S W Y V E 1 367 P A D L A G S G Y C 1 372 G S G Y C G A L W K 1393 K Q K D K E R K A E 1 397 K E R K A E N G P H 1 19 E S I R D H S G QK −1 99 E G I N I S G S F C −1 122 M N T N P S R R P Y −1 136 P S R I FW R Q E K −1 143 Q E K A D G G S C C −1 153 P Q G H A S E A Y K −1 224 PG G G S P R G L G −1 341 H N V L A R G K P Q −1 363 E N G R P A D L A G−1 387 E E G L G G K Q K D −1 210 E K N M K K K I D K −2 317 P N P R H SP S G G −2 319 P R H S P S G G G G −2 3 E H T T K T F P L R −3 186 E K RK E K A E I H −3 349 P Q R K P K S E N N −3

[0837] TABLE XXXVII SEQ. Pos 1 2 3 4 5 6 7 8 9 0 score ID NO. 151P3D4v.1: HLA Peptide Scoring Results A*0202 10-mers SYFPEITHI 293 F A A W KI L G Y D 5 329 E A A V R F V G F P 5 13 C W A D H L S D N Y 3 27 D R AI H I Q A E N 3 32 I Q A E N G P H L L 3 42 V E A E Q A K V F S 3 45 E QA K V F S H R G 3 67 P T A F G S G I H K 3 120 S D A S L V I T D L 3 151V V A L D L Q G V V 3 175 H E A Q Q A C L D Q 3 178 Q Q A C L D Q D A V3 184 Q D A V I A S F D Q 3 187 V I A S F D Q L Y D 3 195 Y D A W R G GL D W 3 205 C N A G W L S D G S 3 273 D E A V Q A C L N D 3 276 V Q A CL N D G A Q 3 282 D G A Q I A K V G Q 3 285 Q I A K V G Q I F A 3 292 IF A A W K I L G Y 3 294 A A W K I L G Y D R 3 304 C D A G W L A D G S 3308 W L A D G S V R Y P 3 328 T E A A V R F V G F 3 330 A A V R F V G FP D 3 14 W A D H L S D N Y T 2 28 R A I H I Q A E N G 2 33 Q A E N G P HL L V 2 43 E A E Q A K V F S H 2 46 Q A K V F S H R G G 2 68 T A F G S GI H K I 2 121 D A S L V I T D L T 2 152 V A L D L Q G V V F 2 176 E A QQ A C L D Q D 2 179 Q A C L D Q D A V I 2 185 D A V I A S F D Q L 2 188I A S F D Q L Y D A 2 196 D A W R G G L D W C 2 206 N A G W L S D G S V2 274 E A V Q A C L N D G 2 277 Q A C L N D G A Q I 2 283 G A Q I A K VG Q I 2 286 I A K V G Q I F A A 2 305 D A G W L A D G S V 2 309 L A D GS V R Y P I 2 15 A D H L S D N Y T L 1 29 A I H I Q A E N G P 1 34 A E NG P H L L V E 1 44 A E Q A K V F S H R 1 47 A K V F S H R G G N 1 69 A FG S G I H K I R 1 122 A S L V I T D L T L 1 153 A L D L Q G V V F P 1177 A Q Q A C L D Q D A 1 180 A C L D Q D A V I A 1 186 A V I A S F D QL Y 1 189 A S F D Q L Y D A W 1 197 A W R G G L D W C N 1 207 A G W L SD G S V Q 1 275 A V Q A C L N D G A 1 278 A C L N D G A Q I A 1 284 A QI A K V G Q I F 1 287 A K V G Q I F A A W 1 295 A W K I L G Y D R C 1306 A G W L A D G S V R 1 310 A D G S V R Y P I S 1 331 A V R F V G F PD K 1 151P3D4 v.2: HLA Peptide Scoring Results A*0202 10-mers SYFPEITHI242 L A A T R A T R I G 5 277 P A A S P A A W L P 5 281 P A A W L P L RT P 5 272 A R A P V P A A S P 4 11 L R A L H I V V E S 3 49 Q G A K D FG H V Q 3 64 K L A Y S N D G E H 3 91 R K A V V V S C E G 3 114 Y L A FL H K R M N 3 144 E K A D G G S C C P 3 155 G H A S E A Y K K V 3 158 SE A Y K K V C L S 3 167 S G A P H E V G W K 3 177 Y Q A V T A T L E E 3180 V T A T L E E K R K 3 190 E K A E I H Y R K N 3 207 K Q A E K N M KK K 3 238 T I A P L A A T R A 3 241 P L A A T R A T R I 3 243 A A T R AT R I G H 3 245 T R A T R I G H P G 3 258 P R A G S S A H R P 3 262 S SA H R P P A L S 3 267 P P A L S A R A P V 3 270 L S A R A P V P A A 3276 V P A A S P A A W L 3 278 A A S P A A W L P L 3 280 S P A A W L P LR T 3 282 A A W L P L R T P W 3 331 K P A R H C Q G Q K 3 343 V L A R GK P Q R K 3 366 R P A D L A G S G Y 3 369 D L A G S G Y C G A 3 376 C GA L W K A I E S 3 380 W K A I E S L E E G 3 399 R K A E N G P H L L 3 12R A L H I V V E S I 2 50 G A K D F G H V Q F 2 65 L A Y S N D G E H W 292 K A V V V S C E G I 2 115 L A F L H K R M N T 2 145 K A D G G S C C PQ 2 156 H A S E A Y K K V C 2 159 E A Y K K V C L S G 2 168 G A P H E VG W K Y 2 178 Q A V T A T L E E K 2 181 T A T L E E K R K E 2 191 K A EI H Y R K N K 2 208 Q A E K N M K K K I 2 239 I A P L A A T R A T 2 246R A T R I G H P G G 2 259 R A G S S A H R P P 2 263 S A H R P P A L S A2 268 P A L S A R A P V P 2 271 S A R A P V P A A S 2 273 R A P V P A AS P A 2 332 P A R H C Q G Q K H 2 344 L A R G K P Q R K P 2 367 P A D LA G S G Y C 2 370 L A G S G Y C G A L 2 377 G A L W K A I E S L 2 381 KA I E S L E E G L 2 13 A L H I V V E S I R 1 51 A K D F G H V Q F V 1 66A Y S N D G E H W T 1 93 A V V V S C E G I N 1 116 A F L H K R M N T N 1146 A D G G S C C P Q G 1 157 A S E A Y K K V C L 1 160 A Y K K V C L SG A 1 169 A P H E V G W K Y Q 1 179 A V T A T L E E K R 1 182 A T L E EK R K E K 1 192 A E I H Y R K N K Q 1 209 A E K N M K K K I D 1 240 A PL A A T R A T R 1 244 A T R A T R I G H P 1 247 A T R I G H P G G R 1260 A G S S A H R P P A 1 264 A H R P P A L S A R 1 269 A L S A R A P VP A 1 274 A P V P A A S P A A 1 279 A S P A A W L P L R 1 283 A W L P LR T P W T 1 333 A R H C Q G Q K H N 1 345 A R G K P Q R K P K 1 368 A DL A G S G Y C G 1 371 A G S G Y C G A L W 1 378 A L W K A I E S L E 1382 A I E S L E E G L G 1

[0838] TABLE XXXVIII SEQ. Pos 1 2 3 4 5 6 7 8 9 0 score ID NO. 151P3D4v.1: HLA Peptide Scoring Results A*0203 10-mers SYFPEITHI 286 I A K V GQ I F A A 19 322 R R R C S P T E A A 19 287 A K V G Q I F A A W 17 323 RR C S P T E A A V 17 6 L L V L I S I C W A 10 20 D N Y T L D H D R A 1025 D H D R A I H I Q A 10 35 E N G P H L L V E A 10 38 P H L L V E A E QA 10 60 P C K F Y R D P T A 10 113 F L K G G S D S D A 10 144 G L E D DT V V V A 10 168 G R Y N L N F H E A 10 171 N L N F H E A Q Q A 10 177 AQ Q A C L D Q D A 10 180 A C L D Q D A V I A 10 188 I A S F D Q L Y D A10 198 W R G G L D W C N A 10 266 H P T K L T Y D E A 10 269 K L T Y D EA V Q A 10 275 A V Q A C L N D G A 10 278 A C L N D G A Q I A 10 285 Q IA K V G Q I F A 10 297 K I L G Y D R C D A 10 301 Y D R C D A G W L A 10321 P R R R C S P T E A 10 343 K L Y G V Y C F R A 10 7 L V L I S I C WA D 9 21 N Y T L D H D R A I 9 26 H D R A I H I Q A E 9 36 N G P H L L VE A E 9 39 H L L V E A E Q A K 9 61 C K F Y R D P T A F 9 114 L K G G SD S D A S 9 145 L E D D T V V V A L 9 169 R Y N L N F H E A Q 9 172 L NF H E A Q Q A C 9 178 Q Q A C L D Q D A V 9 181 C L D Q D A V I A S 9189 A S F D Q L Y D A W 9 199 R G G L D W C N A G 9 267 P T K L T Y D EA V 9 270 L T Y D E A V Q A C 9 276 V Q A C L N D G A Q 9 279 C L N D GA Q I A K 9 298 I L G Y D R C D A G 9 302 D R C D A G W L A D 9 344 L YG V Y C F R A Y 9 8 V L I S I C W A D H 8 22 Y T L D H D R A I H 8 27 DR A I H I Q A E N 8 37 G P H L L V E A E Q 8 40 L L V E A E Q A K V 8 62K F Y R D P T A F G 8 115 K G G S D S D A S L 8 146 E D D T V V V A L D8 170 Y N L N F H E A Q Q 8 173 N F H E A Q Q A C L 8 179 Q A C L D Q DA V I 8 182 L D Q D A V I A S F 8 190 S F D Q L Y D A W R 8 200 G G L DW C N A G W 8 268 T K L T Y D E A V Q 8 271 T Y D E A V Q A C L 8 277 QA C L N D G A Q I 8 280 L N D G A Q I A K V 8 288 K V G Q I F A A W K 8299 L G Y D R C D A G W 8 303 R C D A G W L A D G 8 324 R C S P T E A AV R 8 345 Y G V Y C F R A Y N 8 151P3D4 v.2: HLA Peptide Scoring ResultsA*0203 10-mers SYFPEITHI 235 I F K T I A P L A A 19 270 L S A R A P V PA A 19 274 A P V P A A S P A A 19 265 H R P P A L S A R A 18 236 F K T IA P L A A T 17 271 S A R A P V P A A S 17 275 P V P A A S P A A W 17 4 HT T K T F P L R A 10 42 K V T G I I T Q G A 10 57 V Q F V G S Y K L A 1084 K D K V L L G R K A 10 107 F C R N K L K Y L A 10 137 S R I F W R Q EK A 10 148 G G S C C P Q G H A 10 151 C C P Q G H A S E A 10 160 A Y K KV C L S G A 10 170 P H E V G W K Y Q A 10 173 V G W K Y Q A V T A 10 183T L E E K R K E K A 10 200 K Q L M R L Q K Q A 10 231 G L G F I F K T IA 10 234 F I F K T I A P L A 10 238 T I A P L A A T R A 10 251 G H P G GR T P R A 10 255 G R T P R A G S S A 10 260 A G S S A H R P P A 10 263 SA H R P P A L S A 10 269 A L S A R A P V P A 10 273 R A P V P A A S P A10 324 S G G G G L K K P A 10 336 C Q G Q K H N V L A 10 359 S W Y V E NG R P A 10 362 V E N G R P A D L A 10 369 D L A G S G Y C G A 10 373 S GY C G A L W K A 10 392 G K Q K D K E R K A 10 5 T T K T F P L R A L 9 43V T G I I T Q G A K 9 58 Q F V G S Y K L A Y 9 85 D K V L L G R K A V 9108 C R N K L K Y L A F 9 138 R I F W R Q E K A D 9 149 G S C C P Q G HA S 9 152 C P Q G H A S E A Y 9 161 Y K K V C L S G A P 9 171 H E V G WK Y Q A V 9 174 G W K Y Q A V T A T 9 184 L E E K R K E K A E 9 201 Q LM R L Q K Q A E 9 232 L G F I F K T I A P 9 239 I A P L A A T R A T 9252 H P G G R T P R A G 9 256 R T P R A G S S A H 9 261 G S S A H R P PA L 9 264 A H R P P A L S A R 9 266 R P P A L S A R A P 9 325 G G G G LK K P A R 9 337 Q G Q K H N V L A R 9 360 W Y V E N G R P A D 9 363 E NG R P A D L A G 9 370 L A G S G Y C G A L 9 374 G Y C G A L W K A I 9393 K Q K D K E R K A E 9 6 T K T F P L R A L H 8 44 T G I I T Q G A K D8 59 F V G S Y K L A Y S 8 86 K V L L G R K A V V 8 109 R N K L K Y L AF L 8 139 I F W R Q E K A D G 8 150 S C C P Q G H A S E 8 153 P Q G H AS E A Y K 8 162 K K V C L S G A P H 8 172 E V G W K Y Q A V T 8 175 W KY Q A V T A T L 8 185 E E K R K E K A E I 8 202 L M R L Q K Q A E K 8233 G F I F K T I A P L 8 237 K T I A P L A A T R 8 240 A P L A A T R AT R 8 253 P G G R T P R A G S 8 257 T P R A G S S A H R 8 262 S S A H RP P A L S 8 267 P P A L S A R A P V 8 272 A R A P V P A A S P 8 276 V PA A S P A A W L 8 326 G G G L K K P A R H 8 338 G Q K H N V L A R G 8361 Y V E N G R P A D L 8 364 N G R P A D L A G S 8 371 A G S G Y C G AL W 8 375 Y C G A L W K A I E 8 394 Q K D K E R K A E N 8

[0839] TABLE XXXIX SEQ. Pos 1 2 3 4 5 6 7 8 9 0 score ID NO. 151P3D4v.1: HLA Peptide Scoring Results A3 10-mers SYFPEITHI 288 K V G Q I F AA W K 30 263 Y L I H P T K L T Y 26 331 A V R F V G F P D K 26 186 A V IA S F D Q L Y 24 234 G V R N Y G F W D K 24 39 H L L V E A E Q A K 23 41L V E A E Q A K V F 23 93 D V F V S M G Y H K 23 269 K L T Y D E A V Q A23 260 R F Y Y L I H P T K 22 279 C L N D G A Q I A K 22 111 R V F L K GG S D S 21 166 R L G R Y N L N F H 21 324 R C S P T E A A V R 21 8 V L IS I C W A D H 20 236 R N Y G F W D K D K 20 334 F V G F P D K K H K 20144 G L E D D T V V V A 19 193 Q L Y D A W R G G L 19 343 K L Y G V Y CF R A 19 17 H L S D N Y T L D H 18 74 I H K I R I K W T K 18 128 D L T LE D Y G R Y 18 152 V A L D L Q G V V F 18 153 A L D L Q G V V F P 18 306A G W L A D G S V R 18 313 S V R Y P I S R P R 18 48 K V F S H R G G N V17 91 E V D V F V S M G Y 17 151 V V A L D L Q G V V 17 3 S L L L L V LI S I 16 4 L L L L V L I S I C 16 78 R I K W T K L T S D 16 88 Y L K E VD V F V S 16 113 F L K G G S D S D A 16 124 L V I T D L T L E D 16 129 LT L E D Y G R Y K 16 149 T V V V A L D L Q G 16 155 D L Q G V V F P Y F16 171 N L N F H E A Q Q A 16 231 T V P G V R N Y G F 16 297 K I L G Y DR C D A 16 53 R G G N V T L P C K 15 56 N V T L P C K F Y R 15 76 K I RI K W T K L T 15 125 V I T D L T L E D Y 15 201 G L D W C N A G W L 15208 G W L S D G S V Q Y 15 212 D G S V Q Y P I T K 15 214 S V Q Y P I TK P R 15 275 A V Q A C L N D G A 15 284 A Q I A K V G Q I F 15 7 L V L IS I C W A D 14 11 S I C W A D H L S D 14 40 L L V E A E Q A K V 14 67 PT A F G S G I H K 14 86 S D Y L K E V D V F 14 106 G G Y Q G R V F L K14 140 E V I E G L E D D T 14 141 V I E G L E D D T V 14 159 V V F P Y FP R L G 14 207 A G W L S D G S V Q 14 221 K P R E P C G G Q N 14 292 I FA A W K I L G Y 14 307 G W L A D G S V R Y 14 320 R P R R R C S P T E 1423 T L D H D R A I H I 13 31 H I Q A E N G P H L 13 62 K F Y R D P T A FG 13 83 K L T S D Y L K E V 13 104 T Y G G Y Q G R V F 13 123 S L V I TD L T L E 13 180 A C L D Q D A V I A 13 298 I L G Y D R C D A G 13 5 L LL V L I S I C W 12 6 L L V L I S I C W A 12 9 L I S I C W A D H L 12 29A I H I Q A E N G P 12 34 A E N G P H L L V E 12 44 A E Q A K V F S H R12 77 I R I K W T K L T S 12 81 W T K L T S D Y L K 12 96 V S M G Y H KK T Y 12 122 A S L V I T D L T L 12 130 T L E D Y G R Y K C 12 150 V V VA L D L Q G V 12 187 V I A S F D Q L Y D 12 264 L I H P T K L T Y D 12277 Q A C L N D G A Q I 12 291 Q I F A A W K I L G 12 308 W L A D G S VR Y P 12 314 V R Y P I S R P R R 12 317 P I S R P R R R C S 12 339 D K KH K L Y G V Y 12 22 Y T L D H D R A I H 11 50 F S H R G G N V T L 11 71G S G I H K I R I K 11 79 I K W T K L T S D Y 11 143 E G L E D D T V V V11 161 F P Y F P R L G R Y 11 165 P R L G R Y N L N F 11 181 C L D Q D AV I A S 11 209 W L S D G S V Q Y P 11 227 G G Q N T V P G V R 11 285 Q IA K V G Q I F A 11 318 I S R P R R R C S P 11 325 C S P T E A A V R F 11328 T E A A V R F V G F 11 332 V R F V G F P D K K 11 28 R A I H I Q A EN G 10 30 I H I Q A E N G P H 10 58 T L P C K F Y R D P 10 65 R D P T AF G S G I 10 94 V F V S M G Y H K K 10 95 F V S M G Y H K K T 10 103 K TY G G Y Q G R V 10 158 G V V F P Y F P R L 10 179 Q A C L D Q D A V I 10182 L D Q D A V I A S F 10 239 G F W D K D K S R Y 10 246 S R Y D V F CF T S 10 249 D V F C F T S N F N 10 253 F T S N F N G R F Y 10 257 F N GR F Y Y L I H 10 294 A A W K I L G Y D R 10 315 R Y P I S R P R R R 10333 R F V G F P D K K H 10 340 K K H K L Y G V Y C 10 2 K S L L L L V LI S 9 38 P H L L V E A E Q A 9 73 G I H K I R I K W T 9 138 K C E V I EG L E D 9 170 Y N L N F H E A Q Q 9 190 S F D Q L Y D A W R 9 268 T K LT Y D E A V Q 9 278 A C L N D G A Q I A 9 281 N D G A Q I A K V G 9 287A K V G Q I F A A W 9 303 R C D A G W L A D G 9 330 A A V R F V G F P D9 341 K H K L Y G V Y C F 9 13 C W A D H L S D N Y 8 15 A D H L S D N YT L 8 90 K E V D V F V S M G 8 115 K G G S D S D A S L 8 142 I E G L E DD T V V 8 154 L D L Q G V V F P Y 8 160 V F P Y F P R L G R 8 183 D Q DA V I A S F D 8 197 A W R G G L D W C N 8 218 P I T K P R E P C G 8 223R E P C G G Q N T V 8 229 Q N T V P G V R N Y 8 242 D K D K S R Y D V F8 243 K D K S R Y D V F C 8 299 L G Y D R C D A G W 8 300 G Y D R C D AG W L 8 321 P R R R C S P T E A 8 322 R R R C S P T E A A 8 323 R R C SP T E A A V 8 12 I C W A D H L S D N 7 35 E N G P H L L V E A 7 49 V F SH R G G N V T 7 51 S H R G G N V T L P 7 61 C K F Y R D P T A F 7 63 F YR D P T A F G S 7 66 D P T A F G S G I H 7 69 A F G S G I H K I R 7 75 HK I R I K W T K L 7 99 G Y H K K T Y G G Y 7 101 H K K T Y G G Y Q G 7102 K K T Y G G Y Q G R 7 116 G G S D S D A S L V 7 117 G S D S D A S LV I 7 133 D Y G R Y K C E V I 7 134 Y G R Y K C E V I E 7 195 Y D A W RG G L D W 7 215 V Q Y P I T K P R E 7 219 I T K P R E P C G G 7 224 E PC G G Q N T V P 7 228 G Q N T V P G V R N 7 233 P G V R N Y G F W D 7244 D K S R Y D V F C F 7 247 R Y D V F C F T S N 7 248 Y D V F C F T SN F 7 254 T S N F N G R F Y Y 7 261 F Y Y L I H P T K L 7 311 D G S V RY P I S R 7 319 S R P R R R C S P T 7 327 P T E A A V R F V G 7 336 G FP D K K H K L Y 7 344 L Y G V Y C F R A Y 7 25 D H D R A I H I Q A 6 26H D R A I H I Q A E 6 33 Q A E N G P H L L V 6 42 V K A E Q A K V F S 643 E A E Q A K V F S H 6 55 G N V T L P C K F Y 6 64 Y R D P T A F G S G6 87 D Y L K E V D V F V 6 89 L K E V D V F V S M 6 109 Q G R V F L K GG S 6 110 G R V F L K G G S D 6 118 S D S D A S L V I T 6 119 D S D A SL V I T D 6 127 T D L T L E D Y G R 6 132 E D Y G R Y K C E V 6 145 L ED D T V V V A L 6 147 D D T V V V A L D L 6 157 Q G V V F P Y F P R 6162 P Y F P R L G R Y N 6 169 R Y N L N F H E A Q 6 194 L Y D A W R G GL D 6 199 R G G L D W C N A G 6 200 G G L D W C N A G W 6 203 D W C N AG W L S D 6 222 P R E P C G G Q N T 6 225 P C G G Q N T V P G 6 238 Y GF W D K D K S R 6 245 K S R Y D V F C F T 6 270 L T Y D E A V Q A C 6301 Y D R C D A G W L A 6 304 C D A G W L A D G S 6 312 G S V R Y P I SR P 6 342 H K L Y G V Y C F R 6 1 M K S L L L L V L I 5 10 I S I C W A DH L S 5 19 S D N Y T L D H D R 5 27 D R A I H I Q A E N 5 32 I Q A E N GP H L L 5 47 A K V F S H R G G N 5 52 H R G G N V T L P C 5 54 G G N V TL P C K F 5 57 V T L P C K F Y R D 5 60 P C K F Y R D P T A 5 72 S G I HK I R I K W 5 82 T K L T S D Y L K E 5 84 L T S D Y L K E V D 5 92 V D VF V S M G Y H 5 100 Y H K K T Y G G Y Q 5 105 Y G G Y Q G R V F L 5 107G Y Q G R V F L K G 5 136 R Y K C E V I E G L 5 168 G R Y N L N F H E A5 174 F H E A Q Q A C L D 5 177 A Q Q A C L D Q D A 5 189 A S F D Q L YD A W 5 204 W C N A G W L S D G 5 252 C F T S N F N G R F 5 272 Y D E AV Q A C L N 5 280 L N D G A Q I A K V 5 282 D G A Q I A K V G Q 5 283 GA Q I A K V G Q I 5 295 A W K I L G Y D R C 5 302 D R C D A G W L A D 520 D N Y T L D H D R A 4 37 G P H L L V E A E Q 4 85 T S D Y L K E V D V4 98 M G Y H K K T Y G G 4 112 V F L K G G S D S D 4 135 G R Y K C E V IE G 4 163 Y F P R L G R Y N L 4 164 F P R L G R Y N L N 4 173 N F H E AQ Q A C L 4 175 H E A Q Q A C L D Q 4 178 Q Q A C L D Q D A V 4 185 D AV I A S F D Q L 4 191 F D Q L Y D A W R G 4 196 D A W R G G L D W C 4216 Q Y P I T K P R E P 4 217 Y P I T K P R E P C 4 220 T K P R E P C GG Q 4 230 N T V P G V R N Y G 4 251 F C F T S N F N G R 4 271 T Y D E AV Q A C L 4 273 D E A V Q A C L N D 4 286 I A K V G Q I F A A 4 289 V GQ I F A A W K I 4 296 W K I L G Y D R C D 4 316 Y P I S R P R R R C 4345 Y G V Y C F R A Y N 4 16 D H L S D N Y T L D 3 46 Q A K V F S H R GG 3 80 K W T K L T S D Y L 3 108 Y Q G R V F L K G G 3 114 L K G G S D SD A S 3 120 S D A S L V I T D L 3 126 I T D L T L E D Y G 3 146 E D D TV V V A L D 3 167 L G R Y N L N F H E 3 176 E A Q Q A C L D Q D 3 184 QD A V I A S F D Q 3 202 L D W C N A G W L S 3 205 C N A G W L S D G S 3206 N A G W L S D G S V 3 241 W D K D K S R Y D V 3 258 N G R F Y Y L IH P 3 262 Y Y L I H P T K L T 3 267 P T K L T Y D E A V 3 276 V Q A C LN D G A Q 3 290 G Q I F A A W K I L 3 305 D A G W L A D G S V 3 309 L AD G S V R Y P I 3 310 A D G S V R Y P I S 3 335 V G F P D K K H K L 3337 F P D K K H K L Y G 3 21 N Y T L D H D R A I 2 68 T A F G S G I H KI 2 70 F G S G I H K I R I 2 97 S M G Y H K K T Y G 2 137 Y K C E V I EG L E 2 188 I A S F D Q L Y D A 2 192 D Q L Y D A W R G G 2 198 W R G GL D W C N A 2 210 L S D G S V Q Y P I 2 255 S N F N G R F Y Y L 2 256 NF N G R F Y Y L I 2 265 I H P T K L T Y D E 2 293 F A A W K I L G Y D 2326 S P T E A A V R F V 2 329 E A A V R F V G F P 2 18 L S D N Y T L D HD 1 24 L D H D R A I H I Q 1 36 N G P H L L V E A E 1 45 E Q A K V F S HR G 1 59 L P C K F Y R D P T 1 121 D A S L V I T D L T 1 139 C E V I E GL E D D 1 156 L Q G V V F P Y F P 1 172 L N F H E A Q Q A C 1 211 S D GS V Q Y P I T 1 213 G S V Q Y P I T K P 1 232 V P G V R N Y G F W 1 338P D K K H K L Y G V 1 151P3D4 v.2: HLA Peptide Scoring Results A310-mers SYFPEITHI 111 K L K Y L A F L H K 27 87 V L L G R K A V V V 25343 V L A R G K P Q R K 25 75 T V Y Q D E K Q R K 24 10 P L R A L H I VV E 23 86 K V L L G R K A V V 23 237 K T I A P L A A T R 22 13 A L H I VV E S I R 21 88 L L G R K A V V V S 21 198 K N K Q L M R L Q K 21 331 KP A R H C Q G Q K 21 342 N V L A R G K P Q R 21 19 E S I R D H S G Q K20 36 D L L V P T K V T G 20 102 N I S G S F C R N K 20 269 A L S A R AP V P A 20 284 W L P L R T P W T R 20 64 K L A Y S N D G E H 19 179 A VT A T L E E K R 19 240 A P L A A T R A T R 19 249 R I G H P G G R T P 19322 S P S G G G G L K K 19 33 K K V D L L V P T K 18 45 G I I T Q G A KD F 18 366 R P A D L A G S G Y 18 386 L E E G L G G K Q K 18 154 Q G H AS E A Y K K 17 163 K V C L S G A P H E 17 167 S G A P H E V G W K 17 172E V G W K Y Q A V T 17 182 A T L E E K R K E K 17 202 L M R L Q K Q A EK 17 241 P L A A T R A T R I 17 264 A H R P P A L S A R 17 275 P V P A AS P A A W 17 295 S S C P T S S S T Y 17 372 G S G Y C G A L W K 17 20 SI R D H S G Q K M 16 34 K V D L L V P T K V 16 55 G H V Q F V G S Y K 16165 C L S G A P H E V G 16 189 K E K A E I H Y R K 16 201 Q L M R L Q KQ A E 16 228 S P R G L G F I F K 16 238 T I A P L A A T R A 16 339 Q K HN V L A R G K 16 378 A L W K A I E S L E 16 385 S L E E G L G G K Q 1642 K V T G I I T Q G A 15 83 R K D K V L L G R K 15 136 P S R I F W R QE K 15 191 K A E I H Y R K N K 15 206 Q K Q A E K N M K K 15 207 K Q A EK N M K K K 15 256 R T P R A G S S A H 15 272 A R A P V P A A S P 15 306S L S P Y G P R N P 15 361 Y V E N G R P A D L 15 16 I V V E S I R D H S14 37 L L V P T K V T G I 14 58 Q F V G S Y K L A Y 14 68 S N D G E H WT V Y 14 93 A V V V S C E G I N 14 129 R P Y H F Q V P S R 14 204 R L QK Q A E K N M 14 216 K I D K Y T E S P G 14 315 P L P N P R H S P S 14321 H S P S G G G G L K 14 345 A R G K P Q R K P K 14 352 K P K S E N NS W Y 14 384 E S L E E G L G G K 14 388 E G L G G K Q K D K 14 21 I R DH S G Q K M K 13 43 V T G I I T Q G A K 13 50 G A K D F G H V Q F 13 59F V G S Y K L A Y S 13 94 V V V S C E G I N I 13 100 G I N I S G S F C R13 138 R I F W R Q E K A D 13 153 P Q G H A S E A Y K 13 162 K K V C L SG A P H 13 221 T E S P G G G S P R 13 247 A T R I G H P G G R 13 286 P LR T P W T R P S 13 369 D L A G S G Y C G A 13 7 K T F P L R A L H I 1215 H I V V E S I R D H 12 17 V V E S I R D H S G 12 77 Y Q D E K Q R K DK 12 114 Y L A F L H K R M N 12 120 K R M N T N P S R R 12 134 Q V P S RI F W R Q 12 178 Q A V T A T L E E K 12 205 L Q K Q A E K N M K 12 230 RG L G F I F K T I 12 257 T P R A G S S A H R 12 263 S A H R P P A L S A12 328 G L K K P A R H C Q 12 382 A I E S L E E G L G 12 389 G L G G K QK D K E 12 1 M L E H T T K T F P 11 25 S G Q K M K Q D K K 11 38 L V P TK V T G I I 11 82 Q R K D K V L L G R 11 104 S G S F C R N K L K 11 117F L H K R M N T N P 11 127 S R R P Y H F Q V P 11 143 Q E K A D G G S CC 11 173 V G W K Y Q A V T A 11 175 W K Y Q A V T A T L 11 180 V T A T LE E K R K 11 183 T L E E K R K E K A 11 187 K R K E K A E I H Y 11 193 EI H Y R K N K Q L 11 195 H Y R K N K Q L M R 11 231 G L G F I F K T I A11 234 F I F K T I A P L A 11 243 A A T R A T R I G H 11 250 I G H P G GR T P R 11 255 G R T P R A G S S A 11 271 S A R A P V P A A S 11 320 R HS P S G G G G L 11 371 A G S G Y C G A L W 11 391 G G K Q K D K E R K 11397 K E R K A E N G P H 11 24 H S G Q K M K Q D K 10 31 Q D K K V D L LV P 10 44 T G I I T Q G A K D 10 46 I I T Q G A K D F G 10 49 Q G A K DF G H V Q 10 56 H V Q F V G S Y K L 10 72 E H W T V Y Q D E K 10 95 V VS C E G I N I S 10 99 E G I N I S G S F C 10 142 R Q E K A D G G S C 10186 E K R K E K A E I H 10 210 E K N M K K K I D K 10 225 G G G S P R GL G F 10 227 G S P R G L G F I F 10 266 R P P A L S A R A P 10 273 R A PV P A A S P A 10 276 V P A A S P A A W L 10 288 R T P W T R P S S C 10291 W T R P S S C P T S 10 301 S S T Y D S L S P Y 10 332 P A R H C Q GQ K H 10 337 Q G Q K H N V L A R 10 368 A D L A G S G Y C G 10 9 F P L RA L H I V V 9 52 K D F G H V Q F V G 9 54 F G H V Q F V G S Y 9 81 K Q RK D K V L L G 9 89 L G R K A V V V S C 9 105 G S F C R N K L K Y 9 109 RN K L K Y L A F L 9 110 N K L K Y L A F L H 9 112 L K Y L A F L H K R 9116 A F L H K R M N T N 9 119 H K R M N T N P S R 9 126 P S R R P Y H FQ V 9 150 S C C P Q G H A S E 9 152 C P Q G H A S E A Y 9 157 A S E A YK K V C L 9 159 E A Y K K V C L S G 9 168 G A P H E V G W K Y 9 176 K YQ A V T A T L E 9 194 I H Y R K N K Q L M 9 211 K N M K K K I D K Y 9215 K K I D K Y T E S P 9 244 A T R A T R I G H P 9 248 T R I G H P G GR T 9 254 G G R T P R A G S S 9 268 P A L S A R A P V P 9 278 A A S P AA W L P L 9 279 A S P A A W L P L R 9 283 A W L P L R T P W T 9 293 R PS S C P T S S S 9 311 G P R N P L P N P R 9 326 G G G L K K P A R H 9348 K P Q R K P K S E N 9 364 N G R P A D L A G S 9 383 I E S L E E G LG G 9 6 T K T F P L R A L H 8 12 R A L H I V V E S I 8 28 K M K Q D K KV D L 8 47 I T Q G A K D F G H 8 98 C E G I N I S G S F 8 108 C R N K LK Y L A F 8 122 M N T N P S R R P Y 8 123 N T N P S R R P Y H 8 128 R RP Y H F Q V P S 8 133 F Q V P S R I F W R 8 139 I F W R Q E K A D G 8146 A D G G S C C P Q G 8 188 R K E K A E I H Y R 8 200 K Q L M R L Q KQ A 8 219 K Y T E S P G G G S 8 235 I F K T I A P L A A 8 280 S P A A WL P L R T 8 314 N P L P N P R H S P 8 346 R G K P Q R K P K S 8 354 K SE N N S W Y V E 8 359 S W Y V E N G R P A 8 365 G R P A D L A G S G 8395 K D K E R K A E N G 8 35 V D L L V P T K V T 7 61 G S Y K L A Y S ND 7 65 L A Y S N D G E H W 7 74 W T V Y Q D E K Q R 7 80 E K Q R K D K VL L 7 84 K D K V L L G R K A 7 113 K Y L A F L H K R M 7 160 A Y K K V CL S G A 7 185 E E K R K E K A E I 7 246 R A T R I G H P G G 7 253 P G GR T P R A G S 7 274 A P V P A A S P A A 7 308 S P Y G P R N P L P 7 309P Y G P R N P L P N 7 312 P R N P L P N P R H 7 317 P N P R H S P S G G7 325 G G G G L K K P A R 7 329 L K K P A R H C Q G 7 363 E N G R P A DL A G 7 381 K A I E S L E E G L 7 393 K Q K D K E R K A E 7 399 R K A EN G P H L L 7 11 L R A L H I V V E S 6 27 Q K M K Q D K K V D 6 30 K Q DK K V D L L V 6 90 G R K A V V V S C E 6 97 S C E G I N I S G S 6 135 VP S R I F W R Q E 6 140 F W R Q E K A D G G 6 151 C C P Q G H A S E A 6166 L S G A P H E V G W 6 192 A E I H Y R K N K Q 6 214 K K K I D K Y TE S 6 218 D K Y T E S P G G G 6 220 Y T E S P G G G S P 6 233 G F I F KT I A P L 6 258 P R A G S S A H R P 6 262 S S A H R P P A L S 6 265 H RP P A L S A R A 6 267 P P A L S A R A P V 6 282 A A W L P L R T P W 6285 L P L R T P W T R P 6 287 L R T P W T R P S S 6 300 S S S T Y D S LS P 6 302 S T Y D S L S P Y G 6 304 Y D S L S P Y G P R 6 313 R N P L PN P R H S 6 335 H C Q G Q K H N V L 6 350 Q R K P K S E N N S 6 351 R KP K S E N N S W 6 355 S E N N S W Y V E N 6 379 L W K A I E S L E E 6398 E R K A E N G P H L 6 22 R D H S G Q K M K Q 5 23 D H S G Q K M K QD 5 32 D K K V D L L V P T 5 40 P T K V T G I I T Q 5 60 V G S Y K L A YS N 5 66 A Y S N D G E H W T 5 67 Y S N D G E H W T V 5 69 N D G E H W TV Y Q 5 79 D E K Q R K D K V L 5 91 R K A V V V S C E G 5 101 I N I S GS F C R N 5 124 T N P S R R P Y H F 5 145 K A D G G S C C P Q 5 147 D GG S C C P Q G H 5 156 H A S E A Y K K V C 5 203 M R L Q K Q A E K N 5209 A E K N M K K K I D 5 213 M K K K I D K Y T E 5 236 F K T I A P L AA T 5 270 L S A R A P V P A A 5 281 P A A W L P L R T P 5 294 P S S C PT S S S T 5 305 D S L S P Y G P R N 5 316 L P N P R H S P S G 5 327 G GL K K P A R H C 5 330 K K P A R H C Q G Q 5 340 K H N V L A R G K P 5344 L A R G K P Q R K P 5 362 V E N G R P A D L A 5 373 S G Y C G A L WK A 5 375 Y C G A L W K A I E 5 376 C G A L W K A I E S 5 394 Q K D K ER K A E N 5 3 E H T T K T F P L R 4 4 H T T K T F P L R A 4 18 V E S I RD H S G Q 4 41 T K V T G I I T Q G 4 53 D F G H V Q F V G S 4 63 Y K L AY S N D G E 4 106 S F C R N K L K Y L 4 107 F C R N K L K Y L A 4 118 LH K R M N T N P S 4 121 R M N T N P S R R P 4 130 P Y H F Q V P S R I 4131 Y H F Q V P S R I F 4 137 S R I F W R Q E K A 4 149 G S C C P Q G HA S 4 169 A P H E V G W K Y Q 4 177 Y Q A V T A T L E E 4 197 R K N K QL M R L Q 4 223 S P G G G S P R G L 4 224 P G G G S P R G L G 4 226 G GS P R G L G F I 4 239 I A P L A A T R A T 4 245 T R A T R I G H P G 4252 H P G G R T P R A G 4 259 R A G S S A H R P P 4 260 A G S S A H R PP A 4 261 G S S A H R P P A L 4 277 P A A S P A A W L P 4 292 T R P S SC P T S S 4 318 N P R H S P S G G G 4 319 P R H S P S G G G G 4 334 R HC Q G Q K H N V 4 336 C Q G Q K H N V L A 4 338 G Q K H N V L A R G 4341 H N V L A R G K P Q 4 357 N N S W Y V E N G R 4 377 G A L W K A I ES L 4 390 L G G K Q K D K E R 4 14 L H I V V E S I R D 3 39 V P T K V TG I I T 3 48 T Q G A K D F G H V 3 51 A K D F G H V Q F V 3 62 S Y K L AY S N D G 3 70 D G E H W T V Y Q D 3 85 D K V L L G R K A V 3 92 K A V VV S C E G I 3 96 V S C E G I N I S G 3 103 I S G S F C R N K L 3 115 L AF L H K R M N T 3 125 N P S R R P Y H F Q 3 161 Y K K V C L S G A P 3164 V C L S G A P H E V 3 170 P H E V G W K Y Q A 3 171 H E V G W K Y QA V 3 174 G W K Y Q A V T A T 3 196 Y R K N K Q L M R L 3 217 I D K Y TE S P G G 3 289 T P W T R P S S C P 3 290 P W T R P S S C P T 3 299 T SS S T Y D S L S 3 310 Y G P R N P L P N P 3 324 S G G G G L K K P A 3333 A R H C Q G Q K H N 3 347 G K P Q R K P K S E 3 349 P Q R K P K S EN N 3 360 W Y V E N G R P A D 3 374 G Y C G A L W K A I 3 396 D K E R KA E N G P 3 5 T T K T F P L R A L 2 78 Q D E K Q R K D K V 2 141 W R Q EK A D G G S 2 144 E K A D G G S C C P 2 158 S E A Y K K V C L S 2 190 EK A E I H Y R K N 2 208 Q A E K N M K K K I 2 222 E S P G G G S P R G 2232 L G F I F K T I A P 2 251 G H P G G R T P R A 2 296 S C P T S S S TY D 2 298 P T S S S T Y D S L 2 323 P S G G G G L K K P 2 367 P A D L AG S G Y C 2 370 L A G S G Y C G A L 2 380 W K A I E S L E E G 2 8 T F PL R A L H I V 1 26 G Q K M K Q D K K V 1 29 M K Q D K K V D L L 1 76 V YQ D E K Q R K D 1 132 H F Q V P S R I F W 1 148 G G S C C P Q G H A 1155 G H A S E A Y K K V 1 181 T A T L E E K R K E 1 184 L E E K R K E KA E 1 199 N K Q L M R L Q K Q 1 212 N M K K K I D K Y T 1 229 P R G L GF I F K T 1 242 L A A T R A T R I G 1 303 T Y D S L S P Y G P 1 307 L SP Y G P R N P L 1 353 P K S E N N S W Y V 1 358 N S W Y V E N G R P 1387 E E G L G G K Q K D 1

[0840] TABLE XL SEQ. ID Pos 1 2 3 4 5 6 7 8 9 0 score NO. 151P3D4 v.1:HLA Peptide Scoring Results A26 10-mers SYFPEITHI 155 D L Q G V V F P YF 31 91 E V D V F V S M G Y 29 128 D L T L E D Y G R Y 29 125 V I T D LT L E D Y 25 158 G V V F P Y F P R L 24 231 T V P G V R N Y G F 24 186 AV I A S F D Q L Y 23 242 D K D K S R Y D V F 22 292 I F A A W K I L G Y22 339 D K K H K L Y G V Y 21 31 H I Q A E N G P H L 20 41 L V E A E Q AK V F 20 140 E V I E G L E D D T 20 148 D T V V V A L D L Q 20 244 D K SR Y D V F C F 20 253 F T S N F N G R F Y 20 263 Y L I H P T K L T Y 20 9L I S I C W A D H L 19 93 D V F V S M G Y H K 19 185 D A V I A S F D Q L19 239 G F W D K D K S R Y 19 193 Q L Y D A W R G G L 18 249 D V F C F TS N F N 18 252 C F T S N F N G R F 18 336 G F P D K K H K L Y 18 57 V TL P C K F Y R D 17 173 N F H E A Q Q A C L 17 182 L D Q D A V I A S F 17201 G L D W C N A G W L 17 270 L T Y D E A V Q A C 17 328 T E A A V R FV G F 17 78 R I K W T K L T S D 16 99 G Y H K K T Y G G Y 16 145 L E D DT V V V A L 16 150 V V V A L D L Q G V 16 163 Y F P R L G R Y N L 16 264L I H P T K L T Y D 16 73 G I H K I R I K W T 15 88 Y L K E V D V F V S15 154 L D L Q G V V F P Y 15 161 F P Y F P R L G R Y 15 181 C L D Q D AV I A c 15 229 Q N T V P G V R N Y 15 331 A V R F V G F P D K 15 341 K HK L Y G V Y C F 15 344 L Y G V Y C F R A Y 15 35 E N G P H L L V E A 1448 K V F S H R G G N V 14 83 K L T S D Y L K E V 14 86 S D Y L K E V D VF 14 89 L K E V D V F V S M 14 120 S D A S L V I T D L 14 136 R Y K C EV I E G L 14 144 G L E D D T V V V A 14 147 D D T V V V A L D L 14 153 AL D L Q G V V F P 14 159 V V F P Y F P R L G 14 209 W L S D G S V Q Y P14 219 I T K P R E P C G G 14 234 G V R N Y G F W D K 14 255 S N F N G RF Y Y L 14 308 W L A D G S V R Y P 14 3 S L L L L V L I S I 13 4 L L L LV L I S I C 13 13 C W A D H L S D N Y 13 58 T L P C K F Y R D P 13 61 CK F Y R D P T A F 13 103 K T Y G G Y Q G R V 13 111 R V F L K G G S D S13 124 L V I T D L T L E D 13 165 P R L G R Y N L N F 13 208 G W L S D GS V Q Y 13 284 A Q I A K V G Q I F 13 325 C S P T E A A V R F 13 335 V GF P D K K H K L 13 6 L L V L I S I C W A 12 8 V L I S I C W A D H 12 22Y T L D H D R A I H 12 40 L L V E A E Q A K V 12 43 E A E Q A K V F S H12 67 P T A F G S G I H K 12 94 V F V S M G Y H K K 12 96 V S M G Y H KK T Y 12 104 T Y G G Y Q G R V F 12 113 F L K G G S D S D A 12 123 S L VI T D L T L E 12 129 L T L E D Y G R Y K 12 141 V I E G L E D D T V 12146 E D D T V V V A L D 12 152 V A L D L Q G V V F 12 166 R L G R Y N LN F H 12 176 E A Q Q A C L D Q D 12 187 V I A S F D Q L Y D 12 218 P I TK P R E P C G 12 230 N T V P G V R M Y G 12 248 Y D V F C F T S N F 12256 N F N G R F Y Y L I 12 267 P T K L T Y D E A V 12 271 T Y D E A V QA C L 12 285 Q I A K V G Q I F A 12 288 K V G Q I F A A W K 12 291 Q I FA A W K I L G 12 297 K I L G Y D R C D A 12 307 G W L A D G S V R Y 12 7L V L I S I C W A D 11 11 S I C W A D H L S D 11 16 D H L S D N Y T L D11 29 A I H I Q A E N G P 11 32 I Q A E N G P H L L 11 54 G G N V T L PC K F 11 75 H K I R I K W T K L 11 79 I K W T K L T S D Y 11 81 W T K LT S D Y L K 11 84 L T S D Y L K E V D 11 95 F V S M G Y H K K T 11 115 KG G S D S D A S L 11 119 D S D A S L V I T D 11 126 I T D L T L E D Y G11 149 T V V V A L D L Q G 11 151 V V A L D L Q G V V 11 274 E A V Q A CL N D G 11 275 A V Q A C L N D G A 11 329 E A A V R F V G F P 11 334 F VG F P D K K H K 11 343 K L Y G V Y C F R A 11 23 T L D H D R A I H I 1039 H L L V E A E Q A K 10 55 G N V T L P C K F Y 10 56 N V T L P C K F YR 10 76 K I R I K W T K L T 10 130 T L E D Y G R Y K C 10 171 N L N F HE A Q Q A 10 196 D A W R G G L D W C 10 214 S V Q Y P I T K P R 10 254 TS N F N G R F Y Y 10 269 K L T Y D E A V Q A 10 279 C L N D G A Q I A K10 282 D G A Q I A K V G Q 10 290 G Q I F A A W K I L 10 313 S V R Y P IS R P R 10 317 P I S R P R R R C S 10 327 P T E A A V R F V G 10 17 H LS D N Y T L D H 9 27 D R A I H I Q A E N 9 45 E Q A K V F S H R G 9 50 FS H R G G N V T L 9 68 T A F G S G I H K I 9 80 K W T K L T S D Y L 9105 Y G G Y Q G R V F L 9 132 E D Y G R Y K C E V 9 143 E G L E D D T VV V 9 190 S F D Q L Y D A W R 9 261 F Y Y L I H P T K L 9 280 L N D G AQ I A K V 9 298 I L G Y D R C D A G 9 300 G Y D R C D A G W L 9 333 R FV G F P D K K H 9 5 L L L V L I S I C W 8 15 A D H L S D N Y T L 8 25 DH D R A I H I Q A 8 64 Y R D P T A F G S G 8 87 D Y L K E V D V F V 8112 V F L K G G S D S D 8 122 A S L V I T D L T L 8 160 V F P Y F P R LG R 8 183 D Q D A V I A S F D 8 189 A S F D Q L Y D A W 8 224 E P C G GQ N T V P 8 273 D E A V Q A C L N D 8 287 A K V G Q I F A A W 8 302 D RC D A G W L A D 8 20 D N Y T L D H D R A 7 62 K F Y R D P T A F G 7 69 AF G S G I H K I R 7 90 K E V D V F V S M G 7 107 G Y Q G R V F L K G 7192 D Q L Y D A W R G G 7 203 D W C N A G W L S D 7 226 C G G Q N T V PG V 7 250 V F C F T S N F N G 7 251 F C F T S N F N G R 7 260 R F Y Y LI H P T K 7 305 D A G W L A D G S V 7 311 D G S V R Y P I S R 7 338 P DK K H K L Y G V 7 18 L S D N Y T L D H D 6 26 H D R A I H I Q A E 6 34 AE N G P H L L V E 6 36 N G P H L L V E A E 6 44 A E Q A K V F S H R 6 49V F S H R G G N V T 6 51 S H R G G N V T L P 6 66 D P T A F G S G I H 6102 K K T Y G G Y Q G R 6 118 S D S D A S L V I T 6 121 D A S L V I T DL T 6 133 D Y G R Y K C E V I 6 135 G R Y K C E V I E G 6 211 S D G S VQ Y P I T 6 212 D G S V Q Y P I T K 6 213 G S V Q Y P I T K P 6 247 R YD V F C F T S N 6 259 G R F Y Y L I H P T 6 266 H P T K L T Y D E A 6286 I A K V G Q I F A A 6 295 A W K I L G Y D R C 6 303 R C D A G W L AD G 6 310 A D G S V R Y P I S 6 312 G S V R Y P I S R P 6 326 S P T E AA V R F V 6 1 M K S L L L L V L I 5 12 I C W A D H L S D N 5 24 L D H DR A I H I Q 5 53 R G G N V T L P C K 5 82 T K L T S D Y L K E 5 106 G GY Q G R V F L K 5 108 Y Q G R V F L K G G 5 131 L E D Y G R Y K C E 5168 G R Y N L N F H E A 5 204 W C N A G W L S D G 5 258 N G R F Y Y L IH P 5 283 G A Q I A K V G Q I 5 293 F A A W K I L G Y D 5 2 K S L L L LV L I S 4 42 V E A E Q A K V F S 4 71 G S G I H K I R I K 4 92 V D V F VS M G Y H 4 139 C E V I E G L E D D 4 157 Q G V V F P Y F P R 4 162 P YF P R L G R Y N 4 164 F P R L G R Y N L N 4 172 L N F H E A Q Q A C 4188 I A S F D Q L Y D A 4 205 C N A G W L S D G g 4 215 V Q Y P I T K PR E 4 222 P R E P C G G Q N T 4 232 V P G V R N Y G F W 4 245 K S R Y DV F C F T 4 257 F N G R F Y Y L I H 4 304 C D A G W L A D G S 4 314 V RY P I S R P R R 4 316 Y P I S R P R R R C 4 342 H K L Y G V Y C F R 4 28R A I H I Q A E N G 3 30 I H I Q A E N G P H 3 65 R D P T A F G S G I 370 F G S G I H K I R I 3 72 S G I H K I R I K W 3 77 I R I K W T K L T g3 114 L K G G S D S D A g 3 198 W R G G L D W C N A 3 200 G G L D W C NA G W 3 210 L 3 D G S V Q Y P I 3 221 K P R E P C G G Q N 3 225 P C G GQ N T V P G 3 238 Y G F W D K D K S R 3 243 K D K S R Y D V F C 3 299 LG Y D R C D A G W 3 309 L A D G S V R Y P I 3 318 I S R P R R R C S P 3323 R R C S P T E A A V 3 324 R C S P T E A A V R 3 332 V R F V G F P DK K 3 10 I S I C W A D H L C 2 37 G P H L L V E A E Q 2 46 Q A K V F S HR G G 2 52 H R G G N V T L P C 2 60 P C K F Y R D P T A 2 63 F Y R D P TA F G S 2 85 T S D Y L K E V D V 2 100 Y H K K T Y G G Y Q 2 101 H K K TY G G Y Q G 2 116 G G S D S D A S L V 2 117 G S D S D A S L V I 2 137 YK C E V I E G L E 2 170 Y N L N F H E A Q Q 2 175 H E A Q Q A C L D Q 2178 Q Q A C L D Q D A V 2 180 A C L D Q D A V I A 2 197 A W R G G L D WC N 2 216 Q Y P I T K P R E P 2 217 Y P I T K P R E P C 2 220 T K P R EP C G G Q 2 228 G Q N T V P G V R N 2 236 R N Y G F W D K D K 2 240 F WD K D K S R Y D 2 241 W D K D K S R Y D V 2 276 V Q A C L N D G A Q 2277 Q A C L N D G A Q I 2 296 W K I L G Y D R C D 2 315 R Y P I S R P RR R 2 319 S R P R R R C S P T 2 337 F P D K K H K L Y G 2 340 K K H K LY G V Y C 2 14 W A D H L S D N Y T 1 21 N Y T L D H D R A I 1 38 P H L LV E A E Q A 1 47 A K V F S H R G G N 1 59 L P C K F Y R D P T 1 74 I H KI R I K W T K 1 98 M G Y H K K T Y G G 1 109 Q G R V F L K G G g 1 110 GR V F L K G G S D 1 127 T D L T L E D Y G R 1 134 Y G R Y K C E V I E 1138 K C E V I E G L E D 1 167 L G R Y N L N F H E 1 169 R Y N L N F H EA Q 1 177 A Q Q A C L D Q D A 1 179 Q A C L D Q D A V I 1 184 Q D A V IA S F D Q 1 191 F D Q L Y D A W R G 1 194 L Y D A W R G G L D 1 195 Y DA W R G G L D W 1 199 R G G L D W C N A G 1 206 N A G W L S D G S V 1207 A G W L S D G S V Q 1 223 R E P C G G Q N T V 1 235 V R N Y G F W DK D 1 237 N Y G F W D K D K C 1 246 S R Y D V F C F T S 1 265 I H P T KL T Y D E 1 268 T K L T Y D E A V Q 1 278 A C L N D G A Q I A 1 289 V GQ I F A A W K I 1 294 A A W K I L G Y D R 1 306 A G W L A D G S V R 1320 R P R R R C S P T E 1 321 P R R R C S P T E A 1 322 R R R C S P T EA A 1 345 Y G V Y C F R A Y N 1 151P3D4 v.2: HLA Peptide Scoring ResultsA26 10-mers SYFPEITHI 193 E I H Y R K N K Q L 25 5 T T K T F P L R A L24 298 P T S S S T Y D S L 24 45 G I I T Q G A K D F 22 369 D L A G S GY C G A 22 20 S I R D H S G Q K M 21 233 G F I F K T I A P L 21 56 H V QF V G S Y K L 19 58 Q F V G S Y K L A Y 19 361 Y V E N G R P A D L 19 53D F G H V Q F V G S 18 106 S F C R N K L K Y L 18 204 R L Q K Q A E K NM 18 134 Q V P S R I F W R Q 17 172 E V G W K Y Q A V T 17 398 E R K A EN G P H L 17 59 F V G S Y K L A Y S 16 79 D E K Q R K D K V L 16 108 C RN K L K Y L A F 16 211 K N M K K K I D K Y 16 7 K T F P L R A L H I 1536 D L L V P T K V T G 15 37 L L V P T K V T G I 15 40 P T K V T G I I TQ 15 54 F G H V Q F V G S Y 15 80 E K Q R K D K V L L 15 196 Y R K N K QL M R L 15 244 A T R A T R I G H P 15 301 S S T Y D S L S P Y 15 15 H IV V E S I R D H 14 42 K V T G I I T Q G A 14 50 G A K D F G H V Q F 1495 V V S C E G I N I S 14 109 R N K L K Y L A F L 14 111 K L K Y L A F LH K 14 187 K R K E K A E I H Y 14 190 E K A E I H Y R K N 14 234 F I F KT I A P L A 14 238 T I A P L A A T R A 14 366 R P A D L A G S G Y 14 10P L R A L H I V V E 13 16 I V V E S I R D H S 13 23 D H S G Q K M K Q D13 29 M K Q D K K V D L L 13 47 I T Q G A K D F G H 13 68 S N D G E H WT V Y 13 75 T V Y Q D E K Q R K 13 88 L L G R K A V V V S 13 102 N I S GS F C R N K 13 105 G S F C R N K L K Y 13 123 N T N P S R R P Y H 13 124T N P S R R P Y H F 13 131 Y H F Q V P S R I F 13 138 R I F W R Q E K AD 13 152 C P Q G H A S E A Y 13 182 A T L E E K R K E K 13 216 K I D K YT E S P G 13 237 K T I A P L A A T R 13 256 R T P R A G S S A H 13 275 PV P A A S P A A W 13 288 R T P W T R P S S C 13 291 W T R P S S C P T g13 295 S S C P T S S S T Y 13 352 K P K S E N N S W Y 13 377 G A L W K AI E S L 13 381 K A I E S L E E G L 13 384 E S L E E G L G G K 13 4 H T TK T F P L R A 12 17 V V E S I R D H S G 12 32 D K K V D L L V P T 12 34K V D L L V P T K V 12 94 V V V S C E G I N I 12 163 K V C L S G A P H E12 168 G A P H E V G W K Y 12 180 V T A T L E E K R K 12 220 Y T E S P GG G S P 12 225 G G G S P R G L G F 12 302 S T Y D S L S P Y G 12 342 N VL A R G K P Q R 12 356 E N N S W Y V E N G 12 3 E H T T K T F P L R 11 8T F P L R A L H I V 11 28 K M K Q D K K V D L 11 38 L V P T K V T G I I11 43 V T G I I T Q G A K 11 46 I I T Q G A K D F G 11 70 D G E H W T VY Q D 11 74 W T V Y Q D E K Q R 11 86 K V L L G R K A V V 11 87 V L L GR K A V V V 11 98 C E G I N I S G S F 11 179 A V T A T L E E K R 11 183T L E E K R K E K A 11 222 E S P G G G S P R G 11 223 S P G G G S P R GL 11 227 G S P R G L G F I F 11 247 A T R I G H P G G R 11 306 S L S P YG P R N P 11 320 R H S P S G G G G L 11 343 V L A R G K P Q R K 11 382 AI E S L E E G L G 11 385 S L E E G L G G K Q 11 389 G L G G K Q K D K E11 399 R K A E N G P H L L 11 64 K L A Y S N D G E H 10 93 A V V V S C EG I N 10 100 G I N I S G S F C R 10 103 I S G S F C R N K L 10 114 Y L AF L H K R M N 10 116 A F L H K R M N T N 10 117 F L H K R M N T N P 10122 M N T N P S R R P Y 10 165 C L S G A P H E V G 10 175 W K Y Q A V TA T L 10 201 Q L M R L Q K Q A E 10 241 P L A A T R A T R I 10 249 R I GH P G G R T P 10 261 G S S A H R P P A L 10 276 V P A A S P A A W L 10278 A A S P A A W L P L 10 315 P L P N P R H S P S 10 328 G L K K P A RH C Q 10 335 H C Q G Q K H N V L 10 370 L A G S G Y C G A L 10 378 A L WK A I E S L E 10 13 A L H I V V E S I R 9 19 E S I R D H S G Q K 9 99 EG I N I S G S F C 9 113 K Y L A F L H K R Y 9 147 D G G S C C P Q G H 9157 A S E A Y K K V C L 9 185 E E K R K E K A E I 9 194 I H Y R K N K QL M 9 269 A L S A R A P V P A 9 284 W L P L R T P W T R 9 305 D S L S PY G P R N 9 307 L S P Y G P R N P L 9 1 M L E H T T K T F P 8 2 L E H TT K T F P L 8 97 S C E G I N I S G S 8 101 I N I S G S F C R N 8 144 E KA D G G S C C P 8 159 E A Y K K V C L S G 8 160 A Y K K V C L S G A 8171 H E V G W K Y Q A V 8 207 K Q A E K N M K K K 8 231 G L G F I F K TI A 8 235 I F K T I A P L A A 8 264 A H R P P A L S A R 8 286 P L R T PW T R P S 8 364 N G R P A D L A G S 8 387 E E G L G G K Q K D 8 388 E GL G G K Q K D K 8 11 L R A L H I V V E S 7 61 G S Y K L A Y S N D 7 72 EH W T V Y Q D E K 7 82 Q R K D K V L L G R 7 83 R K D K V L L G R K 7 85D K V L L G R K A V 7 89 L G R K A V V V S C 7 127 S R R P Y H F Q V P 7139 I F W R Q E K A D G 7 155 G H A S E A Y K K V 7 167 S G A P H E V GW K 7 186 E K R K E K A E I H 7 218 D K Y T E S P G G G 7 270 L S A R AP V P A A 7 310 Y G P R N P L P N P 7 323 P S G G G G L K K P 7 338 G QK H N V L A R G 7 363 E N G R P A D L A G 7 396 D K E R K A E N G P 7 31Q D K K V D L L V P 6 33 K K V D L L V P T K 6 51 A K D F G H V Q F V 657 V Q F V G S Y K L A 6 90 G R K A V V V S C E 6 129 R P Y H F Q V P SR 6 132 H F Q V P S R I F W 6 133 F Q V P S R I F W R 6 174 G W K Y Q AV T A T 6 199 N K Q L M R L Q K Q 6 210 E K N M K K K I D K 6 214 K K KI D K Y T E S 6 226 G G S P R G L G F I 6 228 S P R G L G F I F K 6 230R G L G F I F K T I 6 236 F K T I A P L A A T 6 279 A S P A A W L P L R6 337 Q G Q K H N V L A R 6 355 S E N N S W Y V E N 6 380 W K A I E S LE E G 6 12 R A L H I V V E S I 5 41 T K V T G I I T Q G 5 48 T Q G A K DF G H V 5 71 G E H W T V Y Q D E 5 81 K Q R K D K V L L G 5 112 L K Y LA F L H K R 5 158 S E A Y K K V C L g 5 178 Q A V T A T L E E K 5 188 RK E K A E I H Y R 5 197 R K N K Q L M R L Q 5 229 P R G L G F I F K T 5248 T R I G H P G G R T 5 251 G H P G G R T P R A 5 265 H R P P A L S AR A 5 272 A R A P V P A A S P 5 281 P A A W L P L R T P 5 346 R G K P QR K P K S 5 373 S G Y C G A L W K A 5 44 T G I I T Q G A K D 4 52 K D FG H V Q F V G 4 115 L A F L H K R M N T 4 125 N P S R R P Y H F Q 4 146A D G G S C C P Q G 4 150 S C C P Q G H A S E 4 151 C C P Q G H A S E A4 215 K K I D K Y T E S P 4 255 G R T P R A G S S A 4 258 P R A G S S AH R P 4 274 A P V P A A S P A A 4 287 L R T P W T R P S S 4 304 Y D S LS P Y G P R 4 312 P R N P L P N P R H 4 316 L P N P R H S P S G 4 325 GG G G L K K P A R 4 329 L K K P A R H C Q G 4 350 Q R K P K S E N N g 4360 W Y V E N G R P A D 4 394 Q K D K E R K A E N 4 395 K D K E R K A EN G 4 14 L H I V V E S I R D 3 22 R D H S G Q K M K Q 3 69 N D G E H W TV Y Q 3 77 Y Q D E K Q R K D K 3 96 V S C E G I N I S G 3 137 S R I F WR Q E K A 3 141 W R Q E K A D G G g 3 145 K A D G G S C C P Q 3 192 A EI H Y R K N K Q 3 198 K N K Q L M R L Q K 3 205 L Q K Q A E K N M K 3217 I D K Y T E S P G G 3 219 K Y T E S P G G G S 3 221 T E S P G G G SP R 3 232 L G F I F K T I A P 3 252 H P G G R T P R A G 3 283 A W L P LR T P W T 3 292 T R P S S C P T S S 3 293 R P S S C P T S S S 3 303 T YD S L S P Y G P 3 308 S P Y G P R N P L P 3 314 N P L P N P R H S P 3317 P N P R H S P S G G 3 322 S P S G G G G L K K 3 330 K K P A R H C Q3 Q 3 344 L A R G K P Q R K P 3 347 G K P Q R K P K S E 3 351 R K P K SE N N S W 3 371 A G S G Y C G A L W 3 374 G Y C G A L W K A I 3 386 L EE G L G G K Q K 3 391 G G K Q K D K E R K 3 393 K Q K D K E R K A E 3 18V E S I R D H S G Q 2 21 I R D H S G Q K M K 2 24 H S G Q K M K Q D K 225 S G Q K M K Q D K K 2 26 G Q K M K Q D K K V 2 30 K Q D K K V D L L V2 49 Q G A K D F G H V Q 2 55 G H V Q F V G S Y K 2 65 L A Y S N D G E HW 2 76 V Y Q D E K Q R K D 2 78 Q D E K Q R K D K V 2 84 K D K V L L G RK A 2 91 R K A V V V S C E G 2 119 H K R M N T N P S R 2 120 K R M N T NP S R R 2 128 R R P Y H F Q V P S 2 130 P Y H F Q V P S R I 2 136 P S RI F W R Q E K 2 140 F W R Q E K A D G G 2 142 R Q E K A D G G S C 2 143Q E K A D G G S C C 2 156 H A S E A Y K K V C 2 161 Y K K V C L S G A P2 164 V C L S G A P H E V 2 166 L S G A P H E V G W 2 169 A P H E V G WK Y Q 2 173 V G W K Y Q A V T A 2 177 Y Q A V T A T L E E 2 184 L E E KR K E K A E 2 189 K E K A E I H Y R K 2 195 H Y R K N K Q L M R 2 202 LM R L Q K Q A E K 2 203 M R L Q K Q A E K N 2 206 Q K Q A E K N M K K 2208 Q A E K N M K K K I 2 212 N M K K K I D K Y T 2 213 M K K K I D K YT E 2 224 P G G G S P R G L G 2 239 I A P L A A T R A T 2 246 R A T R IG H P G G 2 250 I G H P G G R T P R 2 252 P G G R T P R A G S 2 257 T PR A G S S A H R 2 260 A G S S A H R P P A 2 262 S S A H R P P A L S 2266 R P P A L S A R A P 2 267 P P A L S A R A P V 2 268 P A L S A R A PV P 2 271 S A R A P V P A A S 2 273 R A P V P A A S P A 2 277 P A A S PA A W L P 2 280 S P A A W L P L R T 2 294 P S S C P T S S S T 2 299 T SS S T Y D S L S 2 309 P Y G P R N P L P N 2 313 R N P L P N P R H S 2319 P R H S P S G G G G 2 321 H S P S G G G G L K 2 324 S G G G G L K KP A 2 326 G G G L K K P A R H 2 327 G G L K K P A R H C 2 331 K P A R HC Q G Q K 2 332 P A R H C Q G Q K H 2 334 R H C Q G Q K H N V 2 336 C QG Q K H N V L A 2 348 K P Q R K P K S E N 2 349 P Q R K P K S E N N 2353 P K S E N N S W Y V 2 362 V E N G R P A D L A 2 365 G R P A D L A GS G 2 376 C G A L W K A I E g 2 379 L W K A I E S L E E 2 390 L G G K QK D K E R 2 392 G K Q K D K E R K A 2 6 T K T F P L R A L H 1 27 Q K M KQ D K K V D 1 39 V P T K V T G I I T 1 60 V G S Y K L A Y S N 1 62 S Y KL A Y S N D G 1 63 Y K L A Y S N D G E 1 67 Y S N D G E H W T V 1 73 H WT V Y Q D E K Q 1 92 K A V V V S C E G I 1 110 N K L K Y L A F L H 1 118L H K R M N T N P g 1 121 R M N T N P S R R P 1 126 P S R R P Y H F Q V1 135 V P S R I F W R Q E 1 148 G G S C C P Q G H A 1 149 G S C C P Q GH A C 1 153 P Q G H A S E A Y K 1 154 Q G H A S E A Y K K 1 162 K K V CL S G A P H 1 170 P H E V G W K Y Q A 1 181 T A T L E E K R K E 1 191 KA E I H Y R K M K 1 200 K Q L M R L Q K Q A 1 209 A E K N M K K K I D 1240 A P L A A T R A T R 1 242 L A A T R A T R I G 1 243 A A T R A T R IG H 1 245 T R A T R I G H P G 1 254 G G R T P R A G S S 1 259 R A G S SA H R P P 1 263 S A H R P P A L S A 1 285 L P L R T P W T R P 1 289 T PW T R P S S C P 1 296 S C P T S S S T Y D 1 297 C P T S S S T Y D S 1300 S S S T Y D S L S P 1 318 N P R H S P S G G G 1 333 A R H C Q G Q KH N 1 339 Q K H N V L A R G K 1 340 K H N V L A R G K P 1 345 A R G K PQ R K P K 1 357 N N S W Y V E N G R 1 358 N S W Y V E N G R P 1 367 P AD L A G S G Y C 1 375 Y C G A L W K A I E 1 383 I E S L E E G L G G 1397 K E R K A E N G P H 1

[0841] TABLE XLI SEQ. ID Pos 1 2 3 4 5 6 7 8 9 0 score NO. 151P3D4 v.1:HLA Peptide Scoring Results B*0702 10-mers SYFPEITHI 59 L P C K F Y R DP T 19 326 S P T E A A V R F V 18 266 H P T K L T Y D E A 17 105 Y G G YQ G R V F L 15 145 L E D D T V V V A L 15 224 E P C G G Q N T V P 15 122A S L V I T D L T L 14 320 R P R R R C S P T E 14 337 F P D K K H K L YG 14 115 K G G S D S D A S L 13 221 K P R E P C G G Q N 13 9 L I S I C WA D H L 12 15 A D H L S D N Y T L 12 31 H I Q A E N G P H L 12 32 I Q AE N G P H L L 12 50 F S H R G G N V T L 12 80 K W T K L T S D Y L 12 120S D A S L V I T D L 12 147 D D T V V V A L D L 12 158 G V V F P Y F P RL 12 164 F P R L G R Y N L N 12 217 Y P I T K P R E P C 12 232 V P G V RN Y G F W 12 271 T Y D E A V Q A C L 12 35 E N G P H L L V E A 11 37 G PH L L V E A E Q 11 66 D P T A F G S G I H 11 75 H K I R I K W T K L 11136 R Y K C E V I E 6 L 11 143 E G L E D D T V V V 11 163 Y F P R L G RY N L 11 173 N F H E A Q Q A C L 11 185 D A V I A S F D Q L 11 193 Q L YD A W R G G L 11 201 G L D W C N A G W L 11 245 K S R Y D V F C F T 11255 S N F N G R F Y Y L 11 261 F Y Y L I H P T K L 11 300 G Y D R C D AG W L 11 309 L A D G S V R Y P I 11 316 Y P I S R P R R R C 11 322 R R RC S P T E A A 11 328 T E A A V R F V G F 11 335 V G F P D K K H K L 11 1M K S L L L L V L I 10 70 F G S G I H K I R I 10 76 K I R I K W T K L T10 87 D Y L K E V D V F V 10 104 T Y G G Y Q G R V F 10 117 G S D S D AS L V I 10 118 S D S D A S L V I T 10 142 I K G L E D D T V V 10 144 G LE D D T V V V A 10 155 D L Q G V V F P Y F 10 161 F P Y F P R L G R Y 10165 P R L G R Y N L N F 10 180 A C L D Q D A V I A 10 210 L S D G S V QY P I 10 280 L N D G A Q I A K V 10 290 G Q I F A A W K X L 10 297 K I LG Y D R C D A 10 49 V F S H R G G N V T 9 85 T S D Y L K E V D V 9 89 LK E V D V F V S M 9 103 K T Y G G Y Q G R V 9 121 D A S L V I T D L T 9132 E D Y G R Y K C E V 9 152 V A L D L Q G V V F 9 177 A Q Q A C L D QD A 9 188 I A S F D Q L Y D A 9 198 W R G G L D W C N A 9 226 C G G Q NT V P G V 9 242 D K D K S R Y D V F 9 244 D K S R Y D V F C F 9 269 K LT Y D E A V Q A 9 275 A V Q A C L N D G A 9 284 A Q I A K V G Q I F 9285 Q I A K V G Q I F A 9 321 P R R R C S P T E A 9 323 R R C S P T E AA V 9 343 K L Y G V Y C F R A 9 33 Q A E N G P H L L V 8 41 L V E A E QA K V F 8 61 C K F Y R D P T A F 8 68 T A F G S G I H K I 8 86 S D Y L KE V D V F 8 95 F V S M G Y H K K T 8 113 F L K G G S D S D A 8 116 G G SD S D A S L V 8 133 D Y G R Y K C E V I 8 141 V I E G L E D D T V 8 151V V A L D L Q G V V 8 178 Q Q A C L D Q D A V 8 179 Q A C L D Q D A V I8 211 S D G S V Q Y P I T 8 231 T V P G V R N Y G F 8 256 N F N G R F YY L I 8 278 A C L N D G A Q I A 8 286 I A K V G Q I F A A 8 301 Y D R CD A G W L A 8 325 C S P T E A A V R F 8 341 K H K L Y G V Y C F 8 14 W AD H L S D N Y T 7 21 H Y T L D H D R A I 7 23 T L D H D R A I H I 7 25 DH D R A I H I Q A 7 34 A E N G P H L L V E 7 40 L L V E A E Q A K V 7 48K V F S H R G G N V 7 52 H R G G N V T L P C 7 60 P C K F Y R D P T A 765 R D P T A F G S G I 7 73 G I H K I R I K W T 7 83 K L T S D Y L K E V7 140 E V I E G L E D D T 7 150 V V V A L D L Q G V 7 153 A L D L Q G VV F P 7 168 G R Y N L N F H E A 7 182 L D Q D A V I A S F 7 206 N A G WL S D G S V 7 222 P R E P C G G Q N T 7 223 R E P C G G Q N T V 7 225 PC G G Q N T V P G 7 241 W D K D K S R Y D V 7 248 Y D V F C F T S N F 7259 G R F Y Y L I H P T 7 262 Y Y L I H P T K L T 7 267 P T K L T Y D EA V 7 277 Q A C L N D G A Q I 7 283 G A Q I A K V G Q I 7 287 A K V G QI F A A W 7 305 D A G W L A D G S V 7 319 S R P R R R C S P T 7 338 P DK K H K L Y G V 7 3 S L L L L V L I S I 6 6 L L V L I S I C W A 6 20 D NY T L D H D R A 6 38 P H L L V E A E Q A 6 51 S H R G G N V T L P 6 54 GG N V T L P C K F 6 171 N L N F H E A Q Q A 6 197 A W R G G L D W C N 6252 C F T S N F N G R F 6 289 V G Q I F A A W K I 6 324 R C S P T E A AV R 6 331 A V R F V G F P D K 6 17 H L S D N Y T L D H 5 107 G Y Q G R VF L K G 5 292 I F A A W K I L G Y 5 318 I S R P R R R C S P 5 2 K S L LL L V L I g 4 26 H D R A I H I Q A E 4 42 V E A E Q A K V F S 4 44 A K QA K V F S H R 4 62 K F Y R D P T A F G 4 77 I R I K W T K L T S 4 114 LK G G S D S D A C 4 134 Y G R Y K C E V I E 4 146 E D D T V V V A L D 4243 K D K S R Y D V F C 4 247 R Y D V F C F T S N 4 303 R C D A G W L AD G 4 310 A D G S V R Y P I g 4 329 E A A V R F V G F P 4 340 K K H K LY G V Y C 4 45 E Q A K V F S H R G 3 47 A K V F S H R G G N 3 53 R G G NV T L P C K 3 64 Y R D P T A F G S G 3 69 A F G S G I H K I R 3 84 L T SD Y L K E V D 3 96 V S M G Y H K K T Y 3 119 D S D A S L V I T D 3 124 LV I T D L T L E D 3 138 K C E V I E G L E D 3 160 V F P Y F P R L G R 3166 R L G R Y N L N F H 3 175 H E A Q Q A C L D Q 3 181 C L D Q D A V IA S 3 183 D Q D A V I A S F D 3 186 A V I A S F D Q L Y 3 187 V I A S FD Q L Y D 3 189 A S F D Q L Y D A W 3 195 Y D A W R G G L D W 3 199 R GG L D W C N A G 3 205 C N A G W L S D G S 3 207 A G W L S D G S V Q 3209 W L S D G S V Q Y P 3 234 G V R N Y G F W D K 3 236 R N Y G F W D KD K 3 253 F T S N F N G R F Y 3 257 F N G R F Y Y L I H 3 273 D E A V QA C L N D 3 281 N D G A Q I A K V G 3 282 D G A Q I A K V G Q 3 288 K VG Q I F A A W K 3 294 A A W K I L G Y D R 3 298 I L G Y D R C D A G 3302 D R C D A G W L A D 3 304 C D A G W L A D G S 3 306 A G W L A D G SV R 3 307 G W L A D G S V R Y 3 313 S V R Y P I S R P R 3 314 V R Y P IS R P R R 3 317 P I S R P R R R C S 3 327 P T E A A V R F V G 3 330 A AV R F V G F P D 3 333 R F V G F P D K K H 3 344 L Y G V Y C F R A Y 3 11S I C W A D H L S D 2 12 I C W A D H L S D N 2 22 Y T L D H D R A I H 227 D R A I H I Q A E N 2 29 A I H I Q A E N G P 2 30 I H I Q A E N G P H2 36 N G P H L L V E A E 2 43 E A E Q A K V F S H 2 57 V T L P C K F Y RD 2 63 F Y R D P T A F G S 2 78 R I K W T K L T S D 2 79 I K W T K L T SD Y 2 82 T K L T S D Y L K E 2 88 Y L K E V D V F V S 2 90 K E V D V F VS M G 2 91 E V D V F V S M G Y 2 97 S M G Y H K K T Y G 2 109 Q G R V FL K G G S 2 126 I T D L T L E D Y G 2 135 G R Y K C E V I E G 2 149 T VV V A L D L Q G 2 154 L D L Q G V V F P Y 2 156 L Q G V V F P Y F P 2167 L G R Y N L N F H E 2 169 R Y N L N F H E A Q 2 190 S F D Q L Y D AW R 2 194 L Y D A W R G G L D 2 203 D W C N A G W L S D 2 208 G W L S DG S V Q Y 2 212 D G S V Q Y p I T K 2 214 S V Q Y P I T K P R 2 215 V QY P I T K P R E 2 218 P I T K P R E P C G 2 219 I T K P R E P C G G 2228 G Q N T V P G V R N 2 230 N T V P G V R N Y G 2 240 F W D K D K S RY D 2 258 N G R F Y Y L I H P 2 260 R F Y Y L I H P T K 2 263 Y L I H PT K L T Y 2 264 L I H P T K L T Y D 2 265 I H P T K L T Y D E 2 268 T KL T Y D E A V Q 2 270 L T Y D E A V Q A C 2 276 V Q A C L N D G A Q 2295 A W K I L G Y D R C 2 308 W L A D G S V R Y P 2 311 D G S V R Y P IS R 2 345 Y G V Y C F R A Y N 2 7 L V L I S I C W A D 1 8 V L I S I C WA D H 1 10 I S I C W A D H L S 1 13 C W A D H L S D N Y 1 16 D H L S D NY T L D 1 18 L S D N Y T L D H D 1 28 R A I H I Q A E N G 1 39 H L L V EA E Q A K 1 55 G N V T L P C K F Y 1 67 P T A F G S G I H K 1 71 G S G IH K I R I K 1 72 S G I H K I R I K W 1 74 I H K I R I K W T K 1 98 M G YH K K T Y G G 1 99 G Y H K K T Y G G Y 1 100 Y H K K T Y G G Y Q 1 102 KK T Y G G Y Q G R 1 106 G G Y Q G R V F L K 1 108 Y Q G R V F L K G G 1111 R V F L K G G S D S 1 112 V F L K G G S D S D 1 123 S L V I T D L TL E 1 130 T L E D Y G R Y K C 1 131 L E D Y G R Y K C E 1 157 Q G V V FP Y F P R 1 159 V V F P Y F P R L G 1 162 P Y F P R L G R Y N 1 170 Y NL N F H E A Q Q 1 172 L N F H E A Q Q A C 1 174 F H E A Q Q A C L D 1176 E A Q Q A C L D Q D 1 184 Q D A V I A S F D Q 1 200 G G L D W C N AG W 1 204 W C N A G W L S D G 1 213 G S V Q Y P I T K P 1 227 G G Q N TV P G V R 1 229 Q N T V P G V R N Y 1 237 N Y G F W D K D K S 1 249 D VF C F T S N F N 1 251 F C F T S N F N G R 1 254 T S N F N G R F Y Y 1272 Y D E A V Q A C L N 1 274 E A V Q A C L N D G 1 279 C L N D G A Q IA K 1 291 Q I F A A W K I L G 1 293 F A A W K I L G Y D 1 299 L G Y D RC D A G W 1 315 R Y P I S R P R R R 1 334 F V G F P D K K H K 1 339 D KK H K L Y G V Y 1 342 H X L Y G V Y C F R 1 v.2: HLA Peptide ScoringResults B*0702 10-mers SYFPEITHI 223 S P G G G S P R G L 23 276 V P A AS P A A W L 23 274 A P V P A A S P A A 21 267 P P A L S A R A P V 20 280S P A A W L P L R T 20 278 A A S P A A W L P L 18 9 F P L R A L H I V V17 39 V P T K V T G I I T 17 228 S P R G L G F I F K 16 322 S P S G G GG L K K 16 157 A S E A Y K K V C L 15 240 A P L A A T R A T R 15 261 G SS A H R P P A L 15 252 H P G G R T P R A G 14 257 T P R A G S S A H R 14269 A L S A R A P V P A 14 293 R P S S C P T S S S 14 320 R H S P S G GG G L 14 28 K M K Q D K K V D L 13 80 E K Q R K D K V L L 13 103 I S G SF C R N K L 13 109 R N K L K Y L A F L 13 125 N P S R R P Y H F Q 13 129R P Y H F Q V P S R 13 152 C P Q G H A S E A Y 13 260 A G S S A H R P PA 13 266 R P P A L S A R A P 13 308 S P Y G P R N P L P 13 311 G P R N PL P N P R 13 335 H C Q G Q K H N V L 13 398 E R K A E N G P H L 13 2 L EH T T K T F P L 12 135 V P S R I F W R Q E 12 169 A P H E V G W K Y Q 12175 W K Y Q A V T A T L 12 233 G F I F K T I A P L 12 298 P T S S S T YD S L 12 307 L S P Y G P R N P L 12 314 N P L P N P R H S P 12 316 L P NP R H S P S G 12 318 N P R H S P S G G G 12 331 K P A R H C Q G Q K 12366 R P A D L A G S G Y 12 370 L A G S G Y C G A L 12 399 R K A E N G PH L L 12 5 T T K T F P L R A L 11 29 M K Q D K K V D L L 11 30 K Q D K KV D L L V 11 51 A K D F G H V Q F V 11 79 D E K Q R K D K V L 11 87 V LL G R K A V V V 11 193 E I H Y R K N K Q L 11 283 A W L P L R T P W T 11285 L P L R T P W T R P 11 297 C P T S S S T Y D S 11 348 K P Q R K P KS E N 11 352 K P K S E N N S W Y 11 361 Y V E N G R P A D L 11 381 K A IE S L E E G L 11 7 K T F P L R A L H I 10 42 K V T G I I T Q G A 10 56 HV Q F V G S Y K L 10 66 A Y S N D G E H W T 10 106 3 F C R N K L K Y L10 108 C R N K L K Y L A F 10 172 E V G W K Y Q A V T 10 196 Y R K N K QL M R L 10 226 G G S P R G L G F I 10 230 R G L G F I F K T I 10 235 I FK T I A P L A A 10 251 G H P G G R T P R A 10 270 L S A R A P V P A A 10289 T P W T R P S S C P 10 324 S G G G G L K K P A 10 377 G A L W K A IE S L 10 4 H T T K T F P L R A 9 32 D K K V D L L V P T 9 34 K V D L L VP T K V 9 37 L L V P T K V T G I 9 48 T Q G A K D F G H V 9 86 K V L L GR K A V V 9 160 A Y K K V C L S G A 9 171 H E V G W K Y Q A V 9 173 V GW K Y Q A V T A 9 174 G W K Y Q A V T A T 9 225 G G G S P R G L G F 9238 T I A P L A A T R A 9 239 I A P L A A T R A T 9 241 P L A A T R A TR I 9 336 C Q G Q K H N V L A 9 369 D L A G S G Y C G A 9 374 G Y C G AL W K A I 9 12 R A L H I V V E S I 8 20 S I R D H S G Q K M 8 35 V D L LV P T K V T 8 50 G A K D F G H V Q F 8 85 D K V L L G R K A V 8 107 F CR N K L K Y L A 8 113 K Y L A F L H K R M 8 126 P S R R P Y H F Q V 8148 G G S C C P Q G H A 8 185 E E K R K E K A E I 8 204 R L Q K Q A E KN M 8 231 G L G F I F K T I A 8 234 F I F K T I A P L A 8 236 F K T I AP L A A T 8 248 T R I G H P G G R T 8 263 S A H R P P A L S A 8 265 H RP P A L S A R A 8 273 R A P V P A A S P A 8 294 P S S C P T S S S T 8353 P K S E N N S W Y V 8 362 V E N G R P A D L A 8 38 L V P T K V T G II 7 78 Q D E K Q R K D K V 7 81 K Q R K D K V L L G 7 84 K D K V L L G RK A 7 92 K A V V V S C E G I 7 98 C E G I N I S G S F 7 115 L A F L H KR M N T 7 155 G H A S E A Y K K V 7 194 I H Y R K N K Q L M 7 200 K Q LM R L Q K Q A 7 208 Q A E K N M K K K I 7 212 N M K K K I D K Y T 7 229P R G L G F I F K T 7 255 G R T P R A G S S A 7 290 P W T R P S S C P T7 334 R H C Q G Q K H N V 7 359 S W Y V E N G R P A 7 371 A G S G Y C GA L W 7 392 G K Q K D K E R K A 7 8 T F P L R A L H I V 6 10 P L R A L HI V V E 6 26 G Q K M K Q D K K V 6 45 G I I T Q G A K D F 6 57 V Q F V GS Y K L A 6 67 Y S N D G E H W T V 6 89 L 6 R K A V V V S C 6 94 V V V SC E G I N I 6 124 T N P S R R P Y H F 6 130 P Y H F Q V P S R I 6 131 YH F Q V P S R I F 6 137 S R I F W R Q E K A 6 146 A D G G S C C P Q G 6151 C C P Q G H A S E A 6 164 V C L S G A P H E V 6 170 P H E V G W K YQ A 6 183 T L E E K R K E K A 6 227 G S P R G L G F I F 6 264 A H R P PA L S A R 6 345 A R G K P Q R K P K 6 373 S G Y C G A L W K A 6 58 Q P VG S Y K L A Y 5 68 S H D G E H W T V Y 5 88 L L G R K A V V V S 5 127 SR R P Y H F Q V P 5 145 K A D G G S C C P Q 5 165 C L S G A P H E V G 5195 H Y R K N K Q L M R 5 244 A T R A T R I G H P 5 250 I 6 H P G G R TP R 5 271 S A R A P V P A A S 5 272 A R A P V P A A S P 5 282 A A W L PL R T P W 5 309 P Y G P R N P L P N 5 325 G 6 G G L K K P A R 5 337 Q 6Q K H N V L A R 5 363 E N G R P A D L A G 5 383 I E S L E E G L 6 G 5397 K E R K A E N G P H 5 11 L R A L H I V V E C 4 23 D H S G Q K M K QD 4 31 Q D K K V D L L V P 4 52 K D F G H V Q F V G 4 53 D F G H V Q F VG C 4 69 N D G E H W T V Y Q 4 102 N I S G S F C R N K 4 111 K L K Y L AF L H K 4 128 R R P Y H F Q V P C 4 159 E A Y K K V C L S G 4 166 L S GA P H E V G W 4 177 Y Q A V T A T L E E 4 186 E K R K E K A E I H 4 198K N K Q L M R L Q K 4 216 K I D K Y T E S P G 4 221 T E S P G G G S P R4 222 E S P G G G S P R G 4 224 P G G G S P R G L G 4 247 A T R I G H PG G R 4 279 A S P A A W L P L R 4 286 P L R T P W T R P S 4 291 W T R PS S C P T S 4 300 S S S T Y D S L S P 4 344 L A R G K P Q R K P 4 364 NG R P A D L A G S 4 3 E H T T K T F P L R 3 27 Q K M K Q D K K V D 3 33K K V D L L V P T K 3 47 I T Q G A K D F G H 3 49 Q G A K D F G H V Q 383 R K D K V L L G R K 3 119 H K R M N T N P S R 3 123 N T N P S R R P YH 3 136 P S R I F W R Q E K 3 156 H A S E A Y K K V C 3 162 K K V C L SG A P H 3 167 S G A P H E V G W K 3 176 K Y Q A V T A T L E 3 179 A V TA T L E E K R 3 182 A T L E E K R K E K 3 202 L M R L Q K Q A E K 3 211K N M K K K I D K Y 3 237 K T I A P L A A T R 3 243 A A T R A T R I G H3 253 P G G R T P R A G S 3 258 P R A G S S A H R P 3 259 R A G S S A HR P P 3 275 P V P A A S P A A W 3 287 L R T P W T R P S S 3 304 Y D S LS P Y G P R 3 306 S L S P Y G P R N P 3 323 P S G G G G L K K P 3 346 RG K P Q R K P K S 3 349 P Q R K P K S E N N 3 360 W Y V E N G R P A D 3368 A D L A G S G Y C G 3 372 G S G Y C G A L W K 3 375 Y C G A L W K AI E 3 378 A L W K A I E S L E 3 379 L W K A I E S L E E 3 388 E G L G GK Q K D K 3 389 G L G G K Q K D K E 3 393 K Q K D K E R K A E 3 394 Q KD K E R K A E N 3 1 M L E H T T K T F P 2 6 T K T F P L R A L H 2 13 A LH I V V E S I R 2 16 I V V E S I R D H S 2 18 V K S I R D H S G Q 2 21 IR D H S G Q K M K 2 36 D L L V P T K V T G 2 43 V T G I I T Q G A K 2 46I I T Q G A K D F G 2 59 F V G S Y K L A Y S 2 60 V G S Y K L A Y S N 264 K L A Y S N D G E H 2 77 Y Q D E K Q R K D K 2 82 Q R K D K V L L G R2 90 G R K A V V V S C E 2 91 R K A V V V S C E G 2 93 A V V V S C E G IN 2 95 V V S C E G I N I S 2 97 S C E G I N I S G C 2 99 E G I N I S G SF C 2 101 I N I S G S F C R N 2 104 S G S F C R N K L K 2 105 G S F C RN K L K Y 2 116 A F L H K R M N T N 2 117 F L H K R M N T N P 2 118 L HK R M N T N P S 2 120 K R M N T N P S R R 2 122 M N T N P S R R P Y 2132 H F Q V P S R I F W 2 138 R I F W R Q E K A D 2 139 I F W R Q E K AD G 2 140 F W R Q E K A D G G 2 142 R Q E K A D G G S C 2 144 E K A D GG S C C P 2 150 S C C P Q G H A S E 2 153 P Q G H A S E A Y K 2 158 S KA Y K K V C L S 2 163 K V C L S G A P H E 2 184 L E E K R K E K A E 2188 R K E K A E I H Y R 2 189 K E K A E I H Y R K 2 190 E K A E I H Y RK N 2 191 K A E I H Y R K N K 2 192 A E I H Y R K N K Q 2 197 R K N K QL M R L Q 2 201 Q L M R L Q K Q A E 2 207 K Q A E K N M K K K 2 209 A EK N M K K K I D 2 214 K K K I D K Y T E C 2 215 K K I D K Y T E S P 2217 I D K Y T E S P G G 2 232 L G F I F K T I A P 2 242 L A A T R A T RI G 2 245 T R A T R I G H P G 2 246 R A T R I G H P G G 2 249 R I G H PG G R T P 2 254 G G R T P R A G S S 2 256 R T P R A G S S A H 2 262 S SA H R P P A L S 2 268 P A L S A R A P V P 2 299 T S S S T Y D S L S 2312 P R N P L P N P R H 2 326 G G G L K K P A R H 2 328 G L K K P A R HC Q 2 330 K K P A R H C Q G Q 2 332 P A R H C Q G Q K H 2 333 A R H C QG Q K H N 2 340 K H N V L A R G K P 2 342 N V L A R G K P Q R 2 351 R KP K S E N N S W 2 354 K S E N N S W Y V E 2 355 S E N N S W Y V E N 2356 E N N S W Y V E N G 2 357 N N S W Y V E N G R 2 382 A I E S L E E GL G 2 386 L E E G L G G K Q K 2 387 E E G L G G K Q K D 2 390 L G G K QK D K E R 2 19 E S I R D H S G Q K 1 22 R D H S G Q K M K Q 1 24 H S G QK M K Q D K 1 25 S G Q K M K Q D K K 1 41 T K V T G I I T Q G 1 44 T G II T Q G A K D 1 54 F G H V Q F V G S Y 1 61 G S Y K L A Y S N D 1 63 Y KL A Y S N D G E 1 70 D G E H W T V Y Q D 1 72 E H W T V Y Q D E K 1 110W K L K Y L A F L H 1 114 Y L A F L H K R M N 1 121 R M N T N P S R R P1 133 F Q V P S R I F W R 1 134 Q V P S R I F W R Q 1 143 Q E K A D G GS C C 1 147 D G G S C C P Q G H 1 149 G S C C P Q G H A S 1 154 Q G H AS E A Y K K 1 161 Y K K V C L S G A P 1 180 V T A T L E E K R K 1 187 KR K E K A E I H Y 1 206 Q K Q A E K N M K K 1 210 E K N M K K K I D K 1213 M K K K I D K Y T E 1 219 K Y T E S P G G G C 1 277 P A A S P A A WL P 1 281 P A A W L P L R T P 1 288 R T P W T R P S S C 1 292 T R P s SC P T S S 1 295 S S C P T S S S T Y 1 296 S C P T S S S T Y D 1 301 S ST Y D S L S P Y 1 302 S T Y D S L S P Y G 1 303 T Y D S L S P Y G P 1305 D S L S P Y G P R N 1 310 Y G P R N P L P N P 1 313 R N P L P N P RH S 1 315 P L P N P R H S P S 1 327 G G L K K P A R H C 1 329 L K K P AR H C Q G 1 338 G Q K H N V L A R G 1 341 H N V L A R G K P Q 1 343 V LA R G K P Q R K 1 350 Q R K P K S E N N S 1 365 G R P A D L A G S G 1367 P A D L A G S G Y C 1 376 C G A L W K A I E S 1 380 W K A I E S L EE G 1 384 E S L E E G L G G K 1 395 K D K E R K A E N G 1

[0842] TABLE XLII SEQ. ID Pos 1 2 3 4 5 6 7 8 9 0 score NO. 151P3D4: HLAPeptide Scoring Results B*08 10-mers SYFPEITHI NO DATA

[0843] TABLE XLIII SEQ. ID Pos 1 2 3 4 5 6 7 8 9 0 score NO. 151P3D4:HLA Peptide Scoring Results B*1510 10-mers SYFPEITHI NO DATA

[0844] TABLE XLIV SEQ. ID Pos 1 2 3 4 5 6 7 8 9 0 score NO. 151P3D4: HLAPeptide Scoring Results B*2705 10-mers SYFPEITHI NO DATA

[0845] TABLE XLV SEQ. ID Pos 1 2 3 4 5 6 7 8 9 0 score NO. 151P3D4: HLAPeptide Scoring Results B*2709 10-mers SYFPEITHI NO DATA

[0846] TABLE XLVI SEQ. ID Pos 1 2 3 4 5 6 7 8 9 0 score NO. 151P3D4 v.1:HLA Peptide Scoring Results B*4402 10-mers SYFPEITHI 145 L K D D T V V VA L 26 328 T E A A V R F V G F 22 189 A S F D Q L Y D A W 18 34 A E N GP H L L V E 17 72 S G I H K I R I K W 17 186 A V I A S F D Q L Y 17 287A K V G Q I F A A W 17 335 V G F P D K K H K L 17 68 T A F G S G I H K I16 122 A S L V I T D L T L 16 284 A Q I A K V G Q I F 16 15 A D H L S DN Y T L 15 61 C K F Y R D P T A F 15 75 H K I R I K W T K L 15 96 V S MG Y H K K T Y 15 255 S N F N G R F Y Y L 15 263 Y L I H P T K L T Y 15290 G Q I F A A W K I L 15 336 G F P D K K H K L Y 15 41 L V E A E Q A KV F 14 44 A E Q A K V F S H R 14 86 S D Y L K E V D V F 14 120 S D A S LV I T D L 14 152 V A L D L Q G V V F 14 182 L D Q D A V I A S F 14 292 IF A A W K I L G Y 14 325 C S P T E A A V R F 14 344 L Y G V Y C F R A Y14 1 M K S L L L L V L I 13 3 S L L L L V L I S I 13 21 N Y T L D H D RA I 13 32 I Q A E N G P H L L 13 50 F S H R G G N V T L 13 55 G N V T LP C K F Y 13 90 K E V D V F V S M G 13 91 E V D V F V S M G Y 13 104 T YG G Y Q G R V F 13 131 L E D Y G R Y K C E 13 136 R Y K C E V I E G L 13163 Y F P R L G R Y N L 13 165 P R L G R Y N L N F 13 208 G W L S D G SV Q Y 13 223 R E P C G G Q N T V 13 244 D K S R Y D V F C F 13 253 F T SN F N G R F Y 13 261 F Y Y L I H P T K L 13 300 G Y D R C D A G W L 13341 K H K L Y G V Y C F 13 3 L L L V L I S I C W 12 9 L I S I C W A D HL 12 54 G G N V T L P C K F 12 79 I K W T K L T S D Y 12 105 Y G G Y Q GR V F L 12 125 V I T D L T L E D Y 12 142 I E G L E D D T V V 12 147 D DT V V V A L D L 12 154 L D L Q G V V F P Y 12 155 D L Q G V V F P Y F 12185 D A V I A S F D Q L 12 193 Q L Y D A W R G G L 12 200 G G L D W C NA G W 12 201 G L D W C N A G W L 12 229 Q N T V P G V R N Y 12 231 T V PG V R N Y G F 12 242 D K D K S R Y D V F 12 307 G W L A D G S V R Y 1213 C W A D H L S D N Y 11 23 T L D H D R A I H I 11 42 V H A E Q A K V FS 11 70 F G S G I H K I R I 11 80 K W T K L T S D Y L 11 115 K G G S D SD A S L 11 117 G S D S D A S L V I 11 128 D L T L E D Y G R Y 11 139 C EV I E G L E D D 11 158 G V V F P Y F P R L 11 161 F P Y F P R L G R Y 11173 N F H E A Q Q A C L 11 175 H E A Q Q A C L D Q 11 195 Y D A W R G GL D W 11 239 G F W D K D K S R Y 11 248 Y D V F C F T S N F 11 254 T S NF N G R F Y Y 11 256 N F N G R F Y Y L I 11 271 T Y D E A V Q A C L 11273 D E A V Q A C L N D 11 299 L G Y D R C D A G W 11 309 L A D G S V RY P I 11 339 D K K H K L Y G V Y 11 31 H I Q A E N G P H L 10 65 R D P TA F G S G I 10 99 G y H K K T Y G G Y 10 133 D Y G R Y K C E V I 10 179Q A C L D Q D A V I 10 210 L S D G S V Q Y P I 10 232 V P G V R N Y G FW 10 252 C F T S N F N G R F 10 277 Q A C L N D G A Q I 10 283 G A Q I AK V G Q I 10 289 V G Q I F A A W K I 10 159 V V F P Y F P R L G 8 35 E NG P H L L V E A 7 153 A L D L Q G V V F P 7 180 A C L D Q D A V I A 7124 L V I T D L T L E D 6 143 E G L E D D T V V V 6 146 E D D T V V V AL D 6 162 P y F P R L G R Y N 6 230 N T V P G V R N Y G 6 259 G R F Y YL I H P T 6 278 A C L N D G A Q I A 6 280 L N D G A Q I A K V 6 324 R CS P T E A A V R 6 2 K S L L L L V L I S 5 4 L L L L V L I S I C 5 10 I SI C W A D H L S 5 24 L D H D R A I H I Q 5 26 H D R A I H I Q A E 5 36 NG P H L L V E A E 5 57 V T L P C K F Y R D 5 64 Y R D P T A F G S G 5 69A F G S G I H K I R 5 73 G I H K I R I K W T 5 76 K I R I K W T K L T 577 I R I K W T K L T S 5 118 S D S D A S L V I T 5 140 E V I E G L E D DT 5 181 C L D Q D A V I A S 5 207 A G W L S D G S V Q 5 217 Y P I T K PR E P C 5 251 F C F T S N F N G R 5 262 Y Y L I H P T K L T 5 281 N D GA Q I A K V G 5 286 I A K V G Q I F A A 5 296 W K I L G Y D R C D 5 306A G W L A D G S V R 5 316 Y P I S R P R R R C 5 6 L L V L I S I C W A 417 H L S D N Y T L D H 4 25 D H D R A I H I Q A 4 28 R A I H I Q A E N G4 29 A I H I Q A E N G P 4 38 P H L L V E A E Q A 4 47 A K V F S H R G GN 4 51 S H R G G N V T L P 4 71 G S G I H K I R I K 4 82 T K L T S D Y LK E 4 83 K L T S D Y L K E V 4 95 F V S M G Y H K K T 4 107 G Y Q G R VF L K G 4 108 Y Q G R V F L K G G 4 116 G G S D S D A S L V 4 119 D S DA S L V I T D 4 121 D A S L V I T D L T 4 144 G L E D D T V V V A 4 172L N F H E A Q Q A C 4 176 E A Q Q A C L D Q D 4 197 A W R G G L D W C N4 199 R G G L D W C N A G 4 212 D G S V Q Y P I T K 4 213 G S V Q Y P IT K P 4 214 S V Q Y P I T K P R 4 219 I T K P R E P C G G 4 224 E P C GG Q N T V P 4 238 Y G F W D K D K S R 4 264 L X H P T K L T Y D 4 269 KL T Y D E A V Q A 4 270 L T Y D E A V Q A C 4 274 E A V Q A C L N D G 4279 C L N D G A Q I A K 4 291 Q I F A A W K I L G 4 297 K I L G Y D R CD A 4 302 D R C D A G W L A D 4 312 G S V R Y P I S R P 4 314 V R Y P IS R P R R 4 317 P I S R P R R R C S 4 318 I S R P R R R C S P 4 330 A AV R F V G F P D 4 331 A V R F V G F P D K 4 332 V R F V G F P D K K 4333 R F V G F P D K K H 4 7 L V L I S I C W A D 3 8 V L I S I C W A D H3 18 L S D N Y T L D H D 3 22 Y T L D H D R A I H 3 30 I H I Q A E N G PH 3 33 Q A E N G P H L L V 3 39 H L L V E A E Q A K 3 43 E A E Q A K V FS H 3 45 E Q A K V F S H R G 3 48 K V F S H R G G N V 3 49 V F S H R G GN V T 3 52 H R G G N V T L P C 3 62 K F Y R D P T A F G 3 84 L T S D Y LK E V D 3 111 R V F L K G G S D S 3 114 L K G G S D S D A Q 3 123 S L VI T D L T L E 3 130 T L E D Y G R Y K C 3 132 E D Y G R Y K C E V 3 160V F P Y F P R L G R 3 164 F P R L G R Y N L N 3 166 R L G R Y N L N F H3 168 G R Y N L N F H E A 3 169 R Y N L N F H E A Q 3 170 Y N L N F H EA Q Q 3 171 N L N F H E A Q Q A 3 177 A Q Q A C L D Q D A 3 209 W L S DG S V Q Y P 3 215 V Q Y P I T K P R E 3 216 Q Y P I T K P R E P 3 222 PR E P C G G Q N T 3 225 P C G G Q N T V P G 3 227 G G Q N T V P G V R 3236 R N Y G F W D K D K 3 246 S R Y D V F C F T S 3 249 D V F C F T S NF N 3 258 N G R F Y Y L I H P 3 265 I H P T K L T Y D E 3 267 P T K L TY D E A V 3 268 T K L T Y D E A V Q 3 275 A V Q A C L N D G A 3 294 A AW K I L G Y D R 3 295 A W K I L G Y D R C 3 308 W L A D G S V R Y P 3310 A D G S V R Y P I S 3 311 D G S V R Y P I S R 3 315 R Y P I S R P RR R 3 319 S R P R R R C S P T 3 322 R R R C S P T E A A 3 326 S P T E AA V R F V 3 329 E A A V R F V G F P 3 11 S I C W A D H L S D 2 14 W A DH L S D N Y T 2 16 D H L S D N Y T L D 2 19 S D N Y T L D H D R 2 53 R GG N V T L P C K 2 56 N V T L P C K F Y R 2 58 T L P C K F Y R D P 2 63 FY R D P T A F G S 2 81 W T K L T S D Y L K 2 85 T S D Y L K E V D V 2 87D Y L K E V D V F V 2 88 Y L K E V D V F V S 2 89 L K E V D V F V S M 293 D V F V S M G Y H K 2 94 V F V S M G Y H K K 2 101 H K K T Y G G Y QG 2 103 K T Y G G Y Q G R V 2 106 G G Y Q G R V F L K 2 126 I T D L T LE D Y G 2 127 T D L T L E D Y G R 2 129 L T L E D Y G R Y K 2 135 G R YK C E V I E G 2 138 K C E V I E G L E D 2 141 V I E G L E D D T V 2 148D T V V V A L D L Q 2 149 T V V V A L D L Q G 2 151 V V A L D L Q G V V2 174 F H E A Q Q A C L D 2 178 Q Q A C L D Q D A V 2 183 D Q D A V I AS F D 2 188 I A S F D Q L Y D A 2 190 S F D Q L Y D A W R 2 191 F D Q LY D A W R G 2 192 D Q L Y D A W R G G 2 194 L Y D A W R G G L D 2 196 DA W R G G L D W C 2 203 D W C N A G W L S D 2 220 T K P R E P C G G Q 2221 K P R E P C G G Q N 2 228 G Q N T V P G V R N 2 234 G V R N Y G F WD K 2 237 N Y G F W D K D K S 2 240 F W D K D K S R Y D 2 241 W D K D KS R Y D V 2 243 K D K S R Y D V F C 2 245 K S R Y D V F C F T 2 247 R YD V F C F T S N 2 257 F N G R F Y Y L I H 2 272 Y D E A V Q A C L N 2276 V Q A C L N D G A Q 2 288 K V G Q I F A A W K 2 298 I L G Y D R C DA G 2 303 R C D A G W L A D G 2 304 C D A G W L A D G S 2 313 S V R Y PI S R P R 2 320 R P R R R C S P T E 2 321 P R R R C S P T K A 2 323 R RC S P T E A A V 2 327 P T E A A V R F V G 2 334 F V G F P D K K H K 2337 F P D K K H K L Y G 2 340 K K H K L Y G V Y C 2 343 K L Y G V Y C FR A 2 12 I C W A D H L S D N 1 20 D N Y T L D H D R A 1 37 G P H L L V EA E Q 1 40 L L V E A E Q A K V 1 46 Q A K V F S H R G G 1 59 L P C K F YR D P T 1 60 P C K F Y R D P T A 1 67 P T A F G S G I H K 1 74 I H K I RI K W T K 1 78 R I K W T K L T S D 1 97 S M G Y H K K T Y G 1 98 M G Y HK K T Y G G 1 102 K K T Y G G Y Q G R 1 112 V F L K G G S D S D 1 113 FL K G G S D S D A 1 134 Y G R Y K C E V I E 1 137 Y K C E V I E G L E 1150 V V V A L D L Q G V 1 156 L Q G V V F P Y F P 1 187 V I A S F D Q LY D 1 198 W R G G L D W C N A 1 202 L D W C N A G W L S 1 204 W C N A GW L S D G 1 205 C N A G W L S D G C 1 206 N A G W L S D G S V 1 211 S DG S V Q Y P I T 1 226 C G G Q N T V P G V 1 233 P G V R N Y G F W D 1235 V R N Y G F W D K D 1 260 R F Y Y L I H P T K 1 282 D G A Q I A K VG Q 1 285 Q X A K V G Q I F A 1 293 F A A W K I L G Y D 1 301 Y D R C DA G W L A 1 338 P D K K H K L Y G V 1 342 H K L Y G V Y C F R 1 345 Y GV Y C F R A Y N 1 151P3D4 v.2: HLA Peptide Scoring Results B*440210-mers SYFPEITHI 79 D E K Q R K D K V L 23 2 L E H T T K T F P L 22 185E E K R K E K A E I 21 98 C E G I N I S G S F 20 192 A E I H Y R K N K Q18 278 A A S P A A W L P L 18 45 G I I T Q G A K D F 17 7 K T F P L R AL H I 16 209 A E K N M K K K I D 16 211 K N M K K K I D K Y 16 233 G F IF K T I A P L 16 371 A G S G Y C G A L W 16 5 T T K T F P L R A L 15 80E K Q R K D K V L L 15 106 S F C R N K L K Y L 15 193 E I H Y R K N K QL 15 282 A A W L P L R T P W 15 295 S S C P T S S S T Y 15 58 Q F V G SY K L A Y 14 68 S N D G E H W T V Y 14 105 G S F C R N K L K Y 14 157 AS E A Y K K V C L 14 184 L E E K R K E K A E 14 221 T E S P G G G S P R14 223 S P G G G S P R G L 14 230 R G L G F I F K T I 14 261 G S S A H RP P A L 14 275 P V P A A S P A A W 14 320 R H S P S G G G G L 14 377 G AL W K A I E S L 14 381 K A I E S L E E G L 14 386 L E E G L G G K Q K 14387 E E G L G G K Q K D 14 29 M K Q D K K V D L L 13 50 G A K D F G H VQ F 13 103 I S G S F C R N K L 13 108 C R N K L K Y L A F 13 122 M N T NP S R R P Y 13 131 Y H F Q V P S R I F 13 152 C P Q G H A S E A Y 13 158S E A Y K K V C L S 13 171 H E V G W K Y Q A V 13 226 G G S P R G L G FI 13 307 L S P Y G P R N P L 13 335 H C Q G Q K H N V L 13 355 S E N N SW Y V E N 13 362 V E N G R P A D L A 13 374 G Y C G A L W K A I 13 383 IE S L E E G L G G 13 399 R K A E N G P H L L 13 28 K M K Q D K K V D L12 37 L L V P T K V T G I 12 109 R N K L K Y L A F L 12 124 T N P S R RP Y H F 12 132 H F Q V P S R I F W 12 168 G A P H E V G W K Y 12 175 W KY Q A V T A T L 12 187 K R K E K A E I H Y 12 196 Y R K N K Q L M R L 12227 G S P R G L G F I F 12 301 S S T Y D S L S P Y 12 351 R K P K S E NN S W 12 361 Y V E N G R P A D L 12 370 L A G S G Y C G A L 12 398 E R KA E N G P H L 12 18 V E S I R D H S G Q 11 38 L V P T K V T G I I 11 54F 6 H V Q F V G S Y 11 56 H V Q F V G S Y K L 11 166 L S G A P H E V G W11 189 K E K A E I H Y R K 11 208 Q A E K N M K K K I 11 225 G G G S P RG L G F 11 276 V P A A S P A A W L 11 298 P T S S S T Y D S L 11 352 K PK S E N N S W Y 11 366 R P A D L A G S G Y 11 397 K E R K A E N G P H 1112 R A L H I V V E S I 10 65 L A Y S N D G E H W 10 71 G E H W T V Y Q DE 10 143 Q E K A D G G S C C 10 92 K A V V V S C E G I 9 94 V V V S C EG I N I 9 130 P Y H F Q V P S R I 9 241 P L A A T R A T R I 9 264 A H RP P A L S A R 9 274 A P V P A A S P A A 8 283 A W L P L R T P W T 8 19 ES I R D H S G Q K 7 182 A T L E E K R K E K 7 272 A R A P V P A A S P 7306 S L S P Y G P R N P 7 314 N P L P N P R H S P 7 393 K Q K D K E R KA E 7 35 V D L L V P T K V T 6 66 A Y S N D G E H W T 6 85 D K V L L G RK A V 6 99 E G I N I S G S F C 6 116 A F L H K R M N T N 6 127 S R R P YH F Q V P 6 133 F Q V P S R I F W R 6 138 R I F W R Q E K A D 6 215 K KI D K Y T E S P 6 232 L G F I F K T I A P 6 237 K T I A P L A A T R 6239 I A P L A A T R A T 6 240 A P L A A T R A T R 6 243 A A T R A T R IG H 6 244 A T R A T R I G H P 6 269 A L S A R A P V P A 6 279 A S P A AW L P L R 6 345 A R G K P Q R K P K 6 363 E N G R P A D L A G 6 388 E GL G G K Q K D K 6 3 E H T T K T F P L R 5 10 P L R A L H I V V E 5 23 DH S G Q K M K Q D 5 34 K V D L L V P T K V S 40 P T K V T G I I T Q 5 41T K V T G I I T Q G 5 51 A K D F G H V Q F V 5 52 K D F G H V Q F V G 557 V Q F V G S Y K L A 5 87 V L L G R K A V V V 5 95 V V S C E G I N I S5 97 S C E G I N I S G S 5 104 S G S F C R N K L K 5 123 N T N P S R R PY H 5 137 S R I F W R Q E K A 5 146 A D G G S C C P Q G 5 167 S G A P HE V G W K 5 169 A P H E V G W K Y Q 5 200 K Q L M R L Q K Q A 5 229 P RG L G F I F K T 5 235 I F K T I A P L A A 5 252 H P G G R T P R A G 5260 A G S S A H R P P A 5 266 R P P A L S A R A P 5 309 P Y G P R N P LP N 5 322 S P S G G G G L K K 5 323 P S G G G G L K K P 5 333 A R H C QG Q K H N 5 364 N 6 R P A D L A 6 S 5 8 T F P L R A L H I V 4 9 F P L RA L H I V V 4 14 L H I V V E S I R D 4 15 H I V V E S I R D H 4 27 Q K MK Q D K K V D 4 30 K Q D K K V D L L V 4 33 K K V D L L V P T K 4 44 T 6I I T Q G A K D 4 77 Y Q D E K Q R K D K 4 81 K Q R K D K V L L G 4 86 KV L L G R K A V V 4 88 L L G R K A V V V S 4 101 I N I S G S F C R N 4102 N I S G S F C R N K 4 110 N K L K Y L A F L H 4 112 L K Y L A F L HK R 4 113 K Y L A F L H K R M 4 115 L A F L H K R M N T 4 120 K R M N TN P S R R 4 125 N P S R R P Y H F Q 4 135 V P S R I F W R Q E 4 150 S CC P Q G H A S E 4 156 H A S E A Y K K V C 4 160 A Y K K V C L S G A 4179 A V T A T L E E K R 4 188 R K E K A E T H Y R 4 190 E K A E I H Y RK W 4 191 K A E I H Y R K N K 4 198 K N K Q L M R L Q K 4 199 N K Q L MR L Q K Q 4 201 Q L M R L Q K Q A E 4 207 K Q A E K N M K K K 4 222 E SP G G G S P R G 4 228 S P R G L G F I F K 4 234 F I F K T I A P L A 4238 T I A P L A A T R A 4 247 A T R I G H P G G R 4 248 T R I G H P G GR T 4 250 I G H P G G R T P R 4 256 R T P R A G S S A H 4 263 S A H R PP A L S A 4 265 H R P P A L S A R A 4 270 L S A R A P V P A A 4 271 S AR A P V P A A C 4 284 W L P L R T P W T R 4 287 L R T P W T R P S S 4291 W T R P S S C P T C 4 300 S S S T Y D S L S P 4 313 R N P L P N P RH S 4 324 S 6 G G G L K K P A 4 325 L K K P A R H C Q G 4 337 Q G Q K HN V L A R 4 346 R G K P Q R K P K S 4 347 G K P Q R K P K S E 4 350 Q RK P K S E N N S 4 368 A D L A G S G Y C G 4 378 A L W K A I E S L E 4382 A I E S L E E G L G 4 384 E S L E E G L G G K 4 11 L R A L H I V V ES 3 13 A L H I V V E S I R 3 20 S I R D H S G Q K M 3 21 I R D H S G Q KM K 3 26 G Q K M K Q D K K V 3 31 Q D K K V D L L V P 3 36 D L L V P T KV T G 3 42 K V T G I I T Q G A 3 62 S Y K L A Y S N D G 3 69 N D G E H WT V Y Q 3 72 E H W T V Y Q D E K 3 74 W T V Y Q D E K Q R 3 76 V Y Q D EK Q R K D 3 82 Q R K D K V L L G R 3 84 K D K V L L G R K A 3 93 A V V VS C E G I N 3 111 K L K Y L A F L H K 3 118 L H K R M N T N P S 3 144 EK A D G G S C C P 3 145 K A D G G S C C P Q 3 149 G S C C P Q G H A C 3155 G H A S E A Y K K V 3 159 E A Y K K V C L S G 3 163 K V C L S G A PH E 3 164 V C L S G A P H E V 3 165 C L S G A P H E V G 3 172 E V G W KY Q A V T 3 173 V G W K Y Q A V T A 3 174 G W K Y Q A V T A T 3 176 K YQ A V T A T L E 3 180 V T A T L E E K R K 3 181 T A T L E E K R K E 3186 E K R K E K A E I H 3 203 M R L Q K Q A E K N 3 210 E K N M K K K ID K 3 212 N M K K K I D K Y T 3 224 P G G G S P R G L G 3 236 F K T I AP L A A T 3 242 L A A T R A T R I G 3 251 G H P G G R T P R A 3 255 G RT P R A G S S A 3 258 P R A G S S A H R P 3 262 S S A H R P P A L C 3268 P A L S A R A P V P 3 280 S P A A W L P L R T 3 281 P A A W L P L RT P 3 286 P L R T P W T R P S 3 296 S C P T S S S T Y D 3 308 S P Y G PR N P L P 3 310 Y 6 P R N P L P N P 3 311 G P R N P L P N P R 3 312 P RN P L P N P R H 3 316 L P N P R H S P S G 3 317 P N P R H S P S G G 3325 G 6 G G L K K P A R 3 327 G G L K K P A R H C 3 331 K P A R H C Q GQ K 3 339 Q K H N V L A R G K 3 340 K H N V L A R G K P 3 341 H N V L AR G K P Q 3 342 N V L A R G K P Q R 3 344 L A R G K P Q R K P 3 354 K SE N N S W Y V E 3 356 E N N S W Y V E N G 3 357 N N S W Y V E N G R 3360 W Y V E N G R P A D 3 373 S G Y C G A L W K A 3 376 C G A L W K A IE S 3 4 H T T K T F P L R A 2 6 T K T F P L R A L H 2 25 S 6 Q K M K Q DK K 2 32 D K K V D L L V P T 2 43 V T G I I T Q G A K 2 49 Q 6 A K D F GH V Q 2 53 D F G H V Q F V G c 2 60 V G S Y K L A Y S N 2 67 Y S N D G EH W T V 2 70 D G E H W T V Y Q D 2 83 R K D K V L L G R K 2 89 L G R K AV V V S C 2 107 F C R N K L K Y L A 2 121 R M N T N P S R R P 2 126 P SR R P Y H F Q V 2 128 R R P Y H F Q V P S 2 134 Q V P S R I F W R Q 2151 C C P Q G H A S E A 2 154 Q G H A S E A Y K K 2 161 Y K K V C L S GA P 2 177 Y Q A V T A T L E E 2 178 Q A V T A T L E E K 2 194 I H Y R KN K Q L M 2 197 R K N K Q L M R L Q 2 204 R L Q K Q A E K N M 2 216 K ID K Y T E S P G 2 218 D K Y T E S P G G G 2 245 T R A T R I G H P G 2249 R I G H P G G R T P 2 253 P G G R T P R A G S 2 254 G G R T P R A GS S 2 267 P P A L S A R A P V 2 273 R A P V P A A S P A 2 277 P A A S PA A W L P 2 285 L P L R T P W T R P 2 288 R T P W T R P S S C 2 292 T RP S S C P T S S 2 293 R P S S C P T S S S 2 299 T S S S T Y D S L S 2302 S T Y D S L S P Y G 2 303 T Y D S L S P Y G P 2 304 Y D S L S P Y GP R 2 315 P L P N P R H S P S 2 321 H S P S G G G G L K 2 326 G G G L KK P A R H 2 328 G L K K P A R H C Q 2 330 K K P A R H C Q G Q 2 336 C QG Q K H N V L A 2 343 V L A R G K P Q R K 2 348 K P Q R K P K S E N 2359 S W Y V E N G R P A 2 365 G R P A D L A G S G 2 367 P A D L A G S GY C 2 372 G S G Y C G A L W K 2 385 S L E E G L G G K Q 2 389 G L G G KQ K D K E 2 390 L G G K Q K D K H R 2 392 G K Q K D K E R K A 2 395 K DK E R K A E N G 2 396 D K E R K A E N G P 2 16 I V V E S I R D H S 1 17V V E S I R D H S G 1 22 R D H S G Q K M K Q 1 39 V P T K V T G I I T 147 I T Q G A K D F G H 1 48 T Q G A K D F G H V 1 59 F V G S Y K L A Y S1 63 Y K L A Y S N D G E 1 64 K L A Y S N D G E H 1 73 H W T V Y Q D E KQ 1 78 Q D E K Q R K D K V 1 90 G R K A V V V S C E 1 96 V S C E G I N IS G 1 114 Y L A F L H K R M N 1 129 R P Y H F Q V P S R 1 136 P S R I FW R Q E K 1 139 I F W R Q E K A D G 1 140 F W R Q E K A D G G 1 147 D GG S C C P Q G H 1 148 G G S C C P Q G H A 1 162 K K V C L S G A P H 1170 P H E V G W K Y Q A 1 183 T L E E K R K E K A 1 195 H Y R K N K Q LM R 1 202 L M R L Q K Q A E K 1 205 L Q K Q A E K N M K 1 206 Q K Q A EK N M K K 1 213 M K K K I D K Y T E 1 214 K K K I D K Y T E S 1 219 K YT E S P G G G S 1 246 R A T R I G H P G G 1 259 R A G S S A H R P P 1289 T P W T R P S S C P 1 290 P W T R P S S C P T 1 294 P S S C P T S SS T 1 297 C P T S S S T Y D S 1 305 D S L S P Y G P R N 1 318 N P R H SP S G G G 1 332 P A R H C Q G Q K H 1 334 R H C Q G Q K H N V 1 338 G QK H N V L A R G 1 353 P K S E N N S W Y V 1 358 N S W Y V E N G R P 1369 D L A G S G Y C G A 1 379 L W K A I E S L E E 1 380 W K A I E S L EE G 1 394 Q K D K E R K A E N 1

[0847] TABLE XLVII SEQ. ID Pos 1 2 3 4 5 6 7 8 9 0 score NO. 151P3D4:HLA Peptide Scoring Results B*5101 10-mers SYFPEITHI NO DATA

[0848] TABLE XLVIII SEQ. ID Pos 1 2 3 4 5 6 1 8 9 0 1 2 3 4 5 score NO.151P3D4 v.1: HLA Peptide Scoring Results DRB1*0101 15-mers SYFPEITHI 78R I K W T K L T S D Y L K E V 35 259 G R F Y Y L I H P T K L T Y D 33 61C K F Y R D P T A F G S G I H 30 214 S V Q Y P I T K P R E P C G G 28 7L V L I S I C W A D H L S D N 27 27 D R A I H I Q A E N G P H L L 27 102K K T Y G G Y Q G R V F L K G 27 148 D T V V V A L D L Q G V V F P 27161 P P Y F P R L G R Y N L N F H 27 169 R Y N L N F H E A Q Q A C L D27 109 Q G R V F L K G G S D S D A S 26 267 P T K L T Y D E A V Q A C LN 26 298 I L G Y D R C D A G W L A D G 26 1 M K S L L L L V L I S I C WA 25 39 H L L V E A E Q A K V F S H R 25 139 C E V I E G L E D D T V V VA 25 283 G A Q I A K V G Q I F A A W K 25 4 L L L L V L I S I C W A D HL 24 21 N Y T L D H D R A I H I Q A E 24 29 A I H I Q A E N G P H L L VE 24 36 N G P H L L V E A E Q A K V F 24 46 Q A K V F S H R G G N V T LP 24 150 V V V A L D L Q G V V F P Y F 24 151 V V A L D L Q G V V F P YF P 24 199 R G G L D W C N A G W L S D G 24 229 Q N T V P G V R N Y G FW D K 24 86 S D Y L K E V D V F V S M G Y 23 145 L E D D T V V V A L D LQ G V 23 293 F A A W K I L G Y D R C D A G 23 3 S L L L L V L I S I C WA D H 22 153 A L D L Q G V V F P Y F P R L 22 178 Q Q A C L D Q D A V IA S F D 22 286 I A K V G Q I F A A W K I L G 22 19 S D N Y T L D H D R AI H I Q 21 134 Y G R Y K C E V I E G L E D D 21 74 I H K I R I K W T K LT S D Y 20 85 T S D Y L K E V D V F V S M G 20 154 L D L Q G V V F P Y FP R L G 20 235 V R N Y G F W D K D K S R Y D 20 260 R F Y Y L I H P T KL T Y D E 20 287 A K V 6 Q I F A A W K I L G Y 20 313 S V R Y P I S R PR R R C S P 20 38 P H L L V E A E Q A K V F S H 19 47 A K V F S H R G GN V T L P C 19 92 V D V F V S M G Y H K K T Y G 19 110 G R V F L K G G SD S D A S L 19 160 V F P Y F P R L G R Y N L N F 19 238 Y G F W D K D KS R Y D V F C 19 250 V F C F T S N F N G R F Y Y L 19 254 T S N F N G RF Y Y L I H P T 19 264 L I H P T K L T Y D E A V Q A 19 63 F Y R D P T AF G S G I H K I 18 81 W T K L T S D Y L K E V D V F 18 108 Y Q G R V F LK G G S D S D A 18 131 L E D Y G R Y K C E V I E G L 18 156 L Q G V V FP Y F P R L G R Y 18 171 N L N F H E A Q Q A C L D Q D 18 188 I A S F DQ L Y D A W R G G L 18 191 F D Q L Y D A W R G G L D W C 18 192 D Q L YD A W R G G L D W C N 18 258 N G R F Y Y L I H P T K L T Y 18 269 K L TY D E A V Q A C L N D G 18 273 D E A V Q A C L N D G A Q I A 18 299 L GY D R C D A G W L A D G S 18 302 D R C D A G W L A D G S V R Y 18 329 EA A V R F V G F P D K K H K 18 338 P D K K H K L Y G V Y C F R A 18 56 NV T L P C K F Y R D P T A F 17 71 G S G I H K I R I K W T K L T 17 111 RV F L K G G S D S D A S L V 17 118 S D S D A S L V I T D L T L E 17 123S L V I T D L T L E D Y G R Y 17 149 T V V V A L D L Q G V V F P Y 17206 N A G W L S D G S V Q Y P I T 17 275 A V Q A C L N D G A Q I A K V17 276 V Q A C L N D G A Q I A K V G 17 305 D A G W L A D G S V R Y P IS 17 306 A G W L A D G S V R Y P I S R 17 311 D G S V R Y P I S R P R RR C 17 315 R Y P I S R P R R R C S P T E 17 319 S R P R R R C S P T E AA V R 17 11 S I C W A D H L S D N Y T L D 16 18 L S D N Y T L D H D R AI H I 16 52 H R G G N V T L P C K F Y R D 16 60 P C K F Y R D P T A F GS G I 16 73 G I H K I R I K W T K L T S D 16 83 K L T S D Y L K E V D VF V S 16 89 L K E V D V F V S M G Y H K K 16 91 E V D V F V S M G Y H KK T Y 16 114 L K G G S D S D A S L V I T D 16 142 I E G L E D D T V V VA L D L 16 166 R L G R Y N L N F H E A Q Q A 16 176 E A Q Q A C L D Q DA V I A S 16 179 Q A C L D Q D A V I A S F D Q 16 196 D A W R G G L D WC N A G W L 16 200 G G L D W C N A G W L S D G S 16 203 D W C N A G W LS D G S V Q Y 16 204 W C N A G W L S D G S V Q Y P 16 207 A G W L S D GS V Q Y P I T K 16 246 S R Y D V F C F T S N F N G R 16 282 D G A Q I AK V G Q I F A A W 16 292 I F A A W K I L G Y D R C D A 16 295 A W K I LG Y D R C D A G W L 16 303 R C D A G W L A D G S V R Y P 16 320 R P R RR C S P T E A A V R F 16 323 R R C S P T E A A V R F V G F 16 326 S P TE A A V R F V G F P D K 16 2 K S L L L L V L I S I C W A D 15 30 I H I QA E N G P H L L V E A 15 59 L P C K F Y R D P T A F G S G 15 103 K T Y SG Y Q G R V F L K G G 15 136 R Y K C E V I E G L E D D T V 15 157 Q G VV F P Y F P R L G R Y N 15 212 D G S V Q Y P I T K P R E P C 15 226 C GG Q N T V P G V R N Y G F 15 279 C L N D G A Q I A K V G Q I F 15 6 L LV L I S I C W A D H L S D 14 15 A D H L S D N Y T L D H D R A 14 26 H DR A I H I Q A E N G P H L 14 40 L L V E A E Q A K V F S H R G 14 43 E AE Q A K V F S H R G G N V 14 68 T A F G S G I H K I R I K W T 14 97 S MG Y H K K T Y G G Y Q G R 14 112 V F L K G G S D S D A S L V I 14 115 KG G S D S D A S L V I T D L 14 120 S D A S L V I T D L T L E D Y 14 122A S L V I T D L T L E D Y G R 14 141 V I E G L E D D T V V V A L D 14172 L N F H E A Q Q A C L D Q D A 14 181 C L D Q D A V I A S F D Q L Y14 244 D K S R Y D V F C F T S N F N 14 247 R Y D V F C F T S N F N G RF 14 270 L T Y D E A V Q A C L N D G A 14 308 W L A D G S V R Y P I S RP R 14 119 D S D A S L V I T D L T L E D 13 121 D A S L V I T D L T L ED Y G 13 331 A V R F V G F P D K K H K L Y 13 336 G F P D K K H K L Y GV Y C F 13 107 G Y Q G R V F L K G G S D S D 12 158 G V V F P Y F P R LG R Y N L 12 167 L G R Y N L N F H E A Q Q A C 12 182 L D Q D A V I A SF D Q L Y D 12 183 D Q D A V X A S F D Q L Y D A 12 195 Y D A W R G G LD W C N A G W 12 210 L S D G S V Q Y P I T K P R E 12 223 R E P C G G QN T V P G V R N 12 290 G Q I F A A W K I L G Y D R C 12 5 L L L V L I SI C W A D H L S 11 49 V F S H R G G N V T L P C K F 11 67 P T A F G S GI H K I R I K W 11 93 D V F V S M G Y H K K T Y G G 11 98 M G Y H K K TY G G Y Q G R V 11 105 Y G G Y Q G R V F L K G G S D 11 125 V I T D L TL E D Y G R Y K C 11 201 G L D W C N A G W L S D G S V 11 211 S D G S VQ Y P I T K P R E P 11 216 Q Y P I T K P R E P C G G Q N 11 232 V P G VR N Y G F W D K D K S 11 245 K S R Y D V F C F T S N F N G 11 248 Y D VF C F T S N F N G R F Y 11 256 N F N G R F Y Y L I H P T K L 11 281 N DG A Q I A K V G Q I F A A 11 334 F V G F P D K K H K L Y G V Y 11 339 DK K H K L Y G V Y C F R A Y 11 53 R G G N V T L P C K F Y R D P 10 54 GG N V T L P C K F Y R D P T 10 58 T L P C K F Y R D P T A F G S 10 66 DP T A F G S G I H K I R I K 10 75 H K I R I K W T K L T S D Y L 10 76 KI R I K W T K L T S D Y L K 10 84 L T S D Y L K E V D V F V S M 10 99 GY H K K T Y G G Y Q G R V F 10 126 I T D L T L E D Y G R Y K C E 10 128D L T L E D Y G R Y K C E V I 10 140 E V I E G L E D D T V V V A L 10217 Y P I T K P R E P C G G Q N T 10 219 I T K P R E P C G G Q N T V P10 224 E P C G G Q N T V P G V R N Y 10 237 N Y G F W D K D K S R Y D VF 10 240 F W D K D K S R Y D V F C F T 10 265 I H P T K L T Y D E A V QA C 10 288 K V G Q I F A A W K I L G Y D 10 316 y P I S R P R R R C S PT E A 10 324 R C S P T E A A V R F V G F P 10 332 V R F V G F P D K K HK L Y G 10 13 C W A D H L S D N Y T L D H D 9 35 E N G P H L L V E A E QA K V 9 48 K V F S H R G G N V T L P C K 9 65 R D P T A F G S G I H K IR I 9 95 F V S M G Y H K K T Y G G Y Q 9 106 G G Y Q G R V F L K G G S DS 9 127 T D L T L E D Y G R Y K C E V 9 147 D D T V V V A L D L Q G V VF 9 177 A Q Q A C L D Q D A V I A S F 9 186 A V I A S F D Q L Y D A W RG 9 189 A S F D Q L Y D A W R G G L D 9 193 Q L Y D A W R G G L D W C NA 9 205 C N A G W L S D G S V Q Y P I 9 220 T K P R E P C G G Q N T V PG 9 221 K P R E P C G G Q N T V P G V 9 222 P R E P C G G Q N T V P G VR 9 231 T V P G V R N Y G F W D K D K 9 239 G F W D K D K S R Y D V F CF 9 251 F C F T S N F N G R F Y Y L I 9 262 Y Y L I H P T K L T Y D E AV 9 277 Q A C L N D G A Q I A K V G Q 9 278 A C L N D G A Q I A K V G QI 9 284 A Q I A K V G Q I F A A W K I 9 304 C D A G W L A D G S V R Y PI 9 310 A D G S V R Y P I S R P R R R 9 322 R R R C S P T E A A V R F VG 9 328 T E A A V R F V G F P D K K H 9 333 R F V G F P D K K H K L Y GV 9 8 V L I S I C W A D H L S D N Y 8 9 L I S I C W A D H L S D N Y T 812 I C W A D H L S D N Y T L D H 8 23 T L D H D R A I H I Q A E N G 8 24L D H D R A I H I Q A E N G P 8 31 H I Q A E N G P H L L V E A E 8 33 QA E N G P H L L V E A E Q A 8 34 A E N G P H L L V E A E Q A K 8 37 G PH L L V E A E Q A K V F S 8 64 Y R D P T A F G S G I H K I R 8 87 D Y LK E V D V F V S M G Y H 8 90 K E V D V F V S M G Y H K K T 8 96 V S M GY H K K T Y G G Y Q G 8 101 H K K T Y G G Y Q G R V F L K 8 113 F L K GG S D S D A S L V I T 8 130 T L E D Y G R Y K C E V I E G 8 138 K C E VI E G L E D D T V V V 8 143 E G L E D D T V V V A L D L Q 8 163 Y F P RL G R Y N L N F H E A 8 164 F P R L G R Y N L N F H E A Q 8 175 H E A QQ A C L D Q D A V I A 8 180 A C L D Q D A V I A S F D Q L 8 184 Q D A VI A S F D Q L Y D A W 8 185 D A V I A S F D Q L Y D A W R 8 208 G W L SD G S V Q Y P I T K P 8 242 D K D K S R Y D V F C F T S N 8 253 F T S NF N G R F Y Y L I H P 8 261 F Y Y L I H P T K L T Y D E A 8 274 E A V QA C L N D G A Q I A K 8 280 L N D G A Q I A K V G Q I F A 8 289 V G Q IF A A W K I L G Y D R 8 296 W K I L G Y D R C D A G W L A 8 307 G W L AD G S V R Y P I S R P 8 318 I S R P R R R C S P T E A A V 8 321 P R R RC S P T E A A V R F V 8 327 P T E A A V R F V G F P D K K 8 88 Y L K E VD V F V S M G Y H K 7 146 E D D T V V V A L D L Q G V V 7 285 Q I A K VG Q I F A A W K I L 7 330 A A V R F V G F P D K K H K L 7 50 F S H R G GN V T L P C K F Y 6 51 S H R G G N V T L P C K F Y R 6 77 I R I K W T KL T S D Y L K E 6 135 G R Y K C E V I E G L E D D T 6 144 G L E D D T VV V A L D L Q G 6 173 N F H E A Q Q A C L D Q D A V 6 187 V I A S F D QL Y D A W R G G 6 209 W L S D G S V Q Y P I T K P R 6 213 G S V Q Y P IT K P R E P C G 6 225 P C G G Q N T V P G V R N Y G 6 263 Y L I H P T KL T Y D E A V Q 6 271 T Y D E A V Q A C L N D G A Q 6 309 L A D G S V RY P I S R P R R 6 312 G S V R Y P I S R P R R R C S 6 137 Y K C E V I EG L E D D T V V 5 44 A E Q A K V F S H R G G N V T 4 45 E Q A K V F S HR G G N V T L 4 69 A F G S G I H K I R I K W T K 4 72 S G I H K I R I KW T K L T S 4 100 Y H K K T Y G G Y Q G R V F L 4 25 D H D R A I H I Q AE N G P H 3 133 D Y G R Y K C E V I E G L E D 3 162 P Y F P R L G R Y NL N F H E 3 190 S F D Q L Y D A W R G G L D W 3 227 G G Q N T V P G V RN Y G F W 3 252 C F T S N F N G R F Y Y L I H 3 57 V T L P C K F Y R D PT A F G 2 79 I K W T K L T S D Y L K E V D 2 132 E D Y G R Y K C E V I EG L E 2 165 P R L G R Y N L N F H E A Q Q 2 198 W R G G L D W C N A G WL S D 2 218 P I T K P R E P C G G Q N T V 2 233 P G V R N Y G F W D K DK S R 2 243 K D K S R Y D V F C F T S N F 2 249 D V F C F T S N F N G RF Y Y 2 294 A A W K I L G Y D R C D A G W 2 297 K I L G Y D R C D A G WL A D 2 335 V G F P D K K H K L Y G V Y C 2 14 W A D H L S D N Y T L D HD R 1 17 H L S D N Y T L D H D R A I H 1 28 R A I H I Q A E N G P H L LV 1 32 I Q A E N G P H L L V E A E Q 1 70 F G S G I H K I R I K W T K L1 80 K W T K L T S D Y L K E V D V 1 94 V F V S M G Y H K K T Y G G Y 1124 L V I T D L T L E D Y G R Y K 1 129 L T L E D Y G R Y K C E V I E 1155 D L Q G V V F P Y F P R L G R 1 159 V V F P Y F P R L G R Y N L N 1194 L Y D A W R G G L D W C N A G 1 197 A W R G G L D W C N A G W L S 1202 L D W C N A G W L S D G S V Q 1 228 G Q N T V P G V R N Y G F W D 1234 G V R N Y G F W D K D K S R Y 1 236 R N Y G F W D K D K S R Y D V 1241 W D K D K S R Y D V F C F T S 1 272 Y D E A V Q A C L N D G A Q I 1300 G Y D R C D A G W L A D G S V 1 314 V R Y P I S R P R R R C S P T 1337 P P D K K H K L Y G V Y C F R 1 TABLE XLVIII 151P3D4 v.2: HLAPeptide Scoring Results DRB1*0101 15-mers SYFPEITHI 301 S S T Y D S L SP Y G P R N P 34 32 D K K V D L L V P T K V T G I 33 236 F K T I A P L AA T R A T R I 33 43 V T G I I T Q G A K D F G H V 32 40 P T K V T G I IT Q G A K D F 31 54 F G H V Q F V G S Y K L A Y S 31 128 R R P Y H F Q VP S R I F W R 31 233 G F I F K T I A P L A A T R A 31 158 S E A Y K K VC L S G A P H E 29 217 I D K Y T E S P G G G S P R G 29 18 V E S I R D HS G Q K M K Q D 27 82 Q R K D K V L L G R K A V V V 27 357 N N S W Y V EN G R P A D L A 27 51 A K D F G H V Q F V G S Y K L 26 92 K A V V V S CE G I N I S G S 26 232 L G F I F K T I A P L A A T R 26 247 A T R I G HP G G R T P R A G 26 174 G W K Y Q A V T A T L E E K R 25 202 L M R L QK Q A E K N M K K K 25 239 I A P L A A T R A T R I G H P 25 264 A H R PP A L S A R A P V P A 25 284 W L P L R T P W T R P S S C P 25 5 T T K TF P L R A L H I V V E 24 85 D K V L L G R K A V V V S C E 24 119 H K R MN T N P S R R P Y H F 24 229 P R G L G F I F K T I A P L A 24 281 P A AW L P L R T P W T R P S 24 304 Y D S L S P Y G P R N P L P N 24 377 G AL W K A I E S L E E G L G 24 36 D L L V P T K V T G I I T Q G 22 138 R IF W R Q E K A D G G S C C 22 267 P P A L S A R A P V P A A S P 22 270 LS A R A P V P A A S P A A W 22 359 S W Y V E N G R P A D L A G S 22 116A F L H K R M N T N P S R R P 21 129 R P Y H F Q V P S R I F W R Q 21 35V D L L V P T K V T G I I T Q 20 83 R K D K V L L G R K A V V V S 20 6 TK T F P L R A L H I V V E S 19 98 C E G I N X S G S F C R N K L 19 104 SG S F C R N K L K Y L A F L 19 106 S F C R N K L K Y L A F L H K 19 111K L K Y L A F L H K R M N T N 19 115 L A F L H K R M N T N P S R R 19231 G L G F I F K T I A P L A A T 19 318 N P R H S P S G G G G L K K P19 367 P A D L A G S G Y C G A L W K 19 372 G S G Y C G A L W K A I E SL 19 8 T F P L R A L H I V V E S I R 18 60 V G S Y K L A Y S N D G E H W18 112 L K Y L A F L H K R M N T N P 18 161 y K K V C L S G A P H E V GW 18 171 H E V G W K Y Q A V T A T L E 18 172 E V G W K Y Q A V T A T LE E 18 223 S P G G G S P R G L G F I F K 18 252 H P G G R T P R A G S SA H R 18 338 G Q K H N V L A R G K P Q R K 18 364 N G R P A D L A G S GY C G A 18 384 E S L E E G L G G K Q K D K E 18 2 L E H T T K T F P L RA L H I 17 11 L R A L H I V V E S I R D H S 17 14 L H I V V E S I R D HS G Q K 17 26 G Q K M K Q D K K V D L L V P 17 29 M K Q D K K V D L L VP T K V 17 37 L L V P T K V T G I I T Q G A 17 76 V Y Q D E K Q R K D KV L L G 17 84 K D K V L L G R K A V V V S C 17 90 G R K A V V V S C E GI N I S 17 93 A V V V S C E G I N I S G S F 17 96 V S C E G I N I S G SF C R N 17 109 R N K L K Y L A P L H K R M N 17 137 S R I F W R Q E K AD G G S C 17 160 A Y K K V C L S G A P H E V G 17 181 T A T L E E K R KE K A E I H 17 191 K A E I H Y R K N K Q L M R L 17 200 K Q L M R L Q KQ A E K N M K 17 218 D K Y T E S P G G G S P R G L 17 221 T E S P G G GS P R G L G F I 17 230 R G L G F I F K T I A P L A A 17 253 P G G R T PR A G S S A H R P 17 279 A S P A A W L P L R T P W T R 17 288 R T P W TR P S S C P T S S S 17 337 Q G Q K H N V L A R G K P Q R 17 360 W Y V KN G R P A D L A G S G 17 374 G Y C G A L W K A I E S L E E 17 380 W K AI E S L E E G L G G K Q 17 383 I E S L E H G L G G K Q K D K 17 396 D KE R K A E N G P H L L V E 17 57 V Q F V G S Y K L A Y S N D G 16 86 K VL L G R K A V V V S C E G 16 95 V V S C E G I N I S G S F C R 16 147 D GG S C C P Q G H A S E A Y 16 149 G S C C P Q G H A S E A Y K K 16 199 NK Q L M R L Q K Q A E K N M 16 225 G G G S P R G L G F I F K T I 16 256R T P R A G S S A H R P P A L 16 261 G S S A H R P P A L S A R A P 16266 R P P A L S A R A P V P A A S 16 269 A L S A R A P V P A A S P A A16 271 S A R A P V P A A S P A A W L 16 274 A P V P A A S P A A W L P LR 16 275 P V P A A S P A A W L P L R T 16 307 L S P Y G P R N P L P N PR H 16 311 G P R N P L P N P R H S P S G 16 313 R N P L P N P R H S P SG G G 16 344 L A R G K P Q R K P K S E N N 16 142 R Q E K A D G G S C CP Q G H 15 159 E A Y K K V C L S G A P H E V 15 272 A R A P V P A A S PA A W L P 15 282 A A W L P L R T P W T R P S S 15 290 P W T R P S S C PT S S S T Y 15 295 S S C P T S S S T Y D S L S P 15 356 E N N S W Y V EN G R P A D L 15 397 K E R K A E N G P H L L V E A 15 10 P L R A L H I VV E S I R D H 14 15 H I V V E S I R D H S G Q K M 14 33 K K V D L L V PT K V T G I I 14 97 S C E G I N I S G S F C R N K 14 122 M N T N P S R RP Y H F Q V P 14 162 K K V C L S G A P H E V G W K 14 173 V G W K Y Q AV T A T L E E K 14 193 E I H Y R K N K Q L M R L Q K 14 213 M K K K I DK Y T E S P G G G 14 249 R I G H P G G R T P R A G S S 14 259 R A G S SA H R P P A L S A R 14 260 A G S S A H R P P A L S A R A 14 263 S A H RP P A L S A R A P V P 14 273 R A P V P A A S P A A W L P L 14 287 L R TP W T R P S S C P T S S 14 291 W T R P S S C P T S S S T Y D 14 298 P TS S S T Y D S L S P Y G P 14 333 A R H C Q G Q K H N V L A R G 14 341 HN V L A R G K P Q R K P K S 14 351 R K P K S E N N S W Y V E N G 14 12 RA L H I V V E S I R D H S G 13 212 N M K K K I D K Y T E S P G G 13 245T R A T R I G H P G G R T P R 13 24 H S G Q K M K Q D K K V D L L 12 42K V T G I I T Q G A K D F G H 12 71 G E H W T V Y Q D E K Q R K D 12 74W T V Y Q D E K Q R K D K V L 12 89 L G R K A V V V S C E G I N I 12 184L E E K R K E K A E I H Y R K 12 206 Q K Q A E K N M K K K I D K Y 12210 E K N M K K K I D K Y T E S P 12 342 N V L A R G K P Q R K P K S E12 358 N S W Y V E N G R P A D L A G 12 362 V E N G R P A D L A G S G YC 12 381 K A I E S L E E G L G G K Q K 12 390 L G G K Q K D K E R K A EN G 12 56 H V Q F V G S Y K L A Y S N D 11 64 K L A Y S N D G E H W T VY Q 11 226 G G S P R G L G F I F K T I A 11 321 H S P S G G G G L K K PA R H 11 325 G G G G L K K P A R H C Q G Q 11 326 G G G L K K P A R H CQ G Q K 11 330 K K P A R H C Q G Q K H N V L 11 339 Q K H N V L A R G KP Q R K P 11 3 E H T T K T F P L R A L H I V 10 13 A L H I V V E S I R DH S G Q 10 28 K M K Q D K K V D L L V P T K 10 47 I T Q G A K D F G H VQ F V G 10 48 T Q G A K D F G H V Q F V G S 10 59 F V G S Y K L A Y S ND G E H 10 65 L A Y S N D G E H W T V Y Q D 10 77 Y Q D E K Q R K D K VL L G R 10 105 G S F C R N K L K Y L A F L H 10 107 F C R N K L K Y L AF L H K R 10 108 C R N K L K Y L A F L H K R M 10 114 Y L A F L H K R MN T N P S R 10 124 T N P S R R P Y H F Q V P S R 10 125 N P S R R P Y HF Q V P S R I 10 130 P Y H F Q V P S R I F W R Q E 10 135 V P S R I F WR Q E K A D G G 10 139 I F W R Q E K A D G G S C C P 10 140 F W R Q E KA D G G S C C P Q 10 141 W R Q K K A D G G S C C P Q G 10 152 C P Q G HA S E A Y K K V C L 10 153 P Q G H A S E A Y K K V C L S 10 177 Y Q A VT A T L E E K R K E K 10 178 Q A V T A T L E E K R K E K A 10 183 T L EE K R K E K A E I H Y R 10 195 H Y R K N K Q L M R L Q K Q A 10 198 K NK Q L M R L Q K Q A E K N 10 214 K K K I D K Y T E S P G G G S 10 215 KK I D K Y T E S P G G G S P 10 242 L A A T R A T R I G H P G G R 10 244A T R A T R I G H P G G R T P 10 251 G H P G G R T P R A G S S A H 10289 T P W T R P S S C P T S S S T 10 316 L P N P R H S P S G G G G L K10 317 P N P R H S P S G G G G L K K 10 320 R H S P S G G G G L K K P AR 10 347 6 K P Q R K P K S E N N S W Y 10 376 C G A L W K A I E S L E EG L 10 379 L W K A I E S L E E G L G G K 10 394 Q K D K E R K A E N G PH L L 10 9 F P L R A L H I V V E S I R D 9 23 D H S G Q K M K Q D K K VD L 9 25 S G Q K M K Q D K K V D L L V 9 31 Q D K K V D L L V P T K V TG 9 41 T K V T G I I T Q G A K D F G 9 44 T G I I T Q G A K D F G H V Q9 49 Q G A K D F G H V Q F V G S Y 9 53 D F G H V Q F V G S Y K L A Y 955 G H V Q F V G S Y K L A Y S N 9 73 H W T V Y Q D E K Q R K D K V 9 91R K A V V V S C E G I N I S G 9 100 G I N I S G S F C R N K L K Y 9 101I N I S G S F C R N K L K Y L 9 136 P S R I F W R Q E K A D G G S 9 166L S G A P H E V G W K Y Q A V 9 169 A P H E V G W K Y Q A V T A T 9 194I H Y R K N K Q L M R L Q K Q 9 196 Y R K N K Q L M R L Q K Q A E 9 201Q L M R L Q K Q A E K N M K K 9 211 K N M K K K I D K Y T E S P G 9 219K Y T E S P G G G S P R G L G 9 224 P G G G S P R G L G F I F K T 9 228S P R G L G F I F K T I A P L 9 257 T P R A G S S A H R P P A L S 9 265H R P P A L S A R A P V P A A 9 283 A W L P L R T P W T R P S S C 9 285L P L R T P W T R P S S C P T 9 310 Y G P R N P L P N P R H S P S 9 319P R H S P S G G G G L K K P A 9 322 S P S G G G G L K K P A R H C 9 340K H N V L A R G K P Q R K P K 9 348 K P Q R K P K S E N N S W Y V 9 370L A G S G Y C G A L W K A I E 9 371 A G S G Y C G A L W K A I E S 9 387E E G L G G K Q K D K E R K A 9 388 E G L G G K Q K D K E R K A E 9 393K Q K D K E R K A E N G P H L 9 7 K T F P L R A L H I V V E S I 8 27 Q KM K Q D K K V D L L V P T 8 34 K V D L L V P T K V T G I I T 8 46 I I TQ G A K D F G H V Q F V 8 58 Q F V G S Y K L A Y S N D G E 8 62 S Y K LA Y S N D G E H W T V 8 63 y K L A Y S N D G E H W T V Y 8 72 E H W T VY Q D E K Q R K D K 8 78 Q D E K Q R K D K V L L G R K 8 81 K Q R K D KV L L G R K A V V 8 126 P S R R P Y H F Q V P S R I F 8 132 H F Q V P SR I F W R Q E K A 8 145 K A D G G S C C P Q G H A S E 8 146 A D G G S CC P Q G H A S E A 8 155 G H A S E A Y K K V C L S G A 8 156 K A S E A YK K V C L S G A P 8 163 K V C L S G A P H E V G W K Y 8 167 S G A P H EV G W K Y Q A V T 8 168 G A P H E V G W K Y Q A V T A 8 170 P H E V G WK Y Q A V T A T L 8 188 R K E K A E I H Y R K N K Q L 8 192 A E I H Y RK N K Q L M R L Q 8 197 R K N K Q L M R L Q K Q A E K 8 207 K Q A E K NM K K K I D K Y T 8 216 K I D K Y T E S P G G G S P R 8 235 I F K T I AP L A A T R A T R 8 237 K T I A P L A A T R A T R I G 8 243 A A T R A TR I G H P G G R T 8 246 R A T R I G H P G G R T P R A 8 255 G R T P R AG S S A H R P P A 8 258 P R A G S S A H R P P A L S A 8 268 P A L S A RA P V P A A S P A 8 276 V P A A S P A A W L P L R T P 8 296 S C P T S SS T Y D S L S P Y 8 297 C P T S S S T Y D S L S P Y G 8 303 T Y D S L SP Y G P R N P L P 8 305 D S L S P Y G P R N P L P N P 8 306 S L S P Y GP R N P L P N P R 8 308 S P Y G P R N P L P N P R H S 8 309 P Y G P R NP L P N P R H S P 8 312 P R N P L P N P R H S P S G G 8 315 P L P N P RH S P S G G G G L 8 323 P S G G G G L K K P A R H C Q 8 331 K P A R H CQ G Q K H N V L A 8 332 P A R H C Q G Q K H N V L A R 8 334 R H C Q G QK H N V L A R G K 8 363 E N G R P A D L A G S G Y C G 8 365 G R P A D LA G S G Y C G A L 8 366 R P A D L A G S G Y C G A L W 8 368 A D L A G SG Y C G A L W K A 8 369 D L A G S G Y C G A L W K A I 8 373 S G Y C G AL W K A I E S L E 8 375 Y C G A L W K A I E S L E E G 8 398 E R K A E NG P H L L V E A E 8 400 K A E N G P H L L V E A E Q A 8 21 I R D H S G QK M K Q D K K V 7 88 L L G R K A V V V S C E G I N 7 133 F Q V P S R I FW R Q E K A D 7 148 G G S C C P Q G H A S E A Y K 7 220 Y T E S P G G GS P R G L G F 7 240 A P L A A T R A T R I G H P G 7 250 I G H P G G R TP R A G S S A 7 254 G G R T P R A G S S A H R P P 7 294 P S S C P T S SS T Y D S L S 7 314 N P L P N P R H S P S G G G G 7 324 S G G G G L K KP A R H C Q G 7 345 A R G K P Q R K P K S E N N S 7 17 V V E S I R D H SG Q K M K Q 6 52 K D F G H V Q F V G S Y K L A 6 67 Y S N D G E H W T VY Q D E K 6 70 D G E H W T V Y Q D E K Q R K 6 118 L H K R M N T N P S RR P Y H 6 150 S C C P Q G H A S E A Y K K V 6 175 W K Y Q A V T A T L EE K R K 6 278 A A S P A A W L P L R T P W T 6 286 P L R T P W T R P S SC P T S 6 292 T R P S S C P T S S S T Y D S 6 293 R P S S C P T S S S TY D S L 6 300 S S S T Y D S L S P Y G P R N 6 16 I V V E S I R D H S G QK M K 5 134 Q V P S R I F W R Q E K A D G 5 179 A V T A T L E E K R K EK A E 5 395 K D K E R K A E N G P H L L V 5 79 D E K Q R K D K V L L G RK A 4 87 V L L G R K A V V V S C E G I 4 189 K E K A E I H Y R K N K Q LM 4 234 F I F K T I A P L A A T R A T 4 80 E K Q R K D K V L L G R K A V3 117 F L H K R M N T N P S R R P Y 3 182 A T L E E K R K E K A E I H Y3 186 E K R K E K A E I H Y R K N K 3 209 A E K N M K K K I D K Y T E S3 241 P L A A T R A T R I G H P G G 3 343 V L A R G K P Q R K P K S E N3 349 P Q R K P K S E N N S W Y V E 3 378 A L W K A I E S L E E G L G G3 382 A I E S L E E G L G G K Q K D 3 385 S L E E G L G G K Q K D K E R3 391 G G K Q K D K E R K A E N G P 3 4 H T T K T F P L R A L H I V V 219 E S I R D H S G Q K M K Q D K 2 38 L V P T K V T G I I T Q G A K 2 39V P T K V T G I I T Q G A K D 2 45 G I I T Q G A K D F G H V Q F 2 61 GS Y K L A Y S N D G E H W T 2 102 N I S G S F C R N K L K Y L A 2 110 NK L K Y L A F L H K R M N T 2 120 K R M N T N P S R R P Y H F Q 2 157 AS E A Y K K V C L S G A P H 2 164 V C L S G A P H E V G W K Y Q 2 203 MR L Q K Q A E K N M K K K I 2 205 L Q K Q A E K N M K K K I D K 2 208 QA E K N M K K K I D K Y T E 2 227 G S P R G L G F I F K T I A P 2 248 TR I G H P G G R T P R A G S 2 262 S S A H R P P A L S A R A P V 2 280 SP A A W L P L R T P W T R P 2 328 G L K K P A R H C Q G Q K H N 2 335 HC Q G Q K H N V L A R G K P 2 355 S E N N S W Y V E N G R P A D 2 392 GK Q K D K E R K A E N G P H 2 1 M L E H T T K T F P L R A L H 1 20 S I RD H S G Q K M K Q D K K 1 30 K Q D K K V D L L V P T K V T 1 66 A Y S ND G E H W T V Y Q D E 1 75 T V Y Q D E K Q R K D K V L L 1 103 I S G S FC R N K L K Y L A F 1 113 K Y L A F L H K R M N T N P S 1 121 R M N T NP S R R P Y H F Q V 1 131 Y H F Q V P S R I F W R Q E K 1 154 Q G H A SE A Y K K V C L S G 1 165 C L S G A P H E V G W K Y Q A 1 176 K Y Q A VT A T L E E K R K E 1 180 V T A T L E E K R K E K A E I 1 185 E E K R KE K A E I H Y R K N 1 187 K R K E K A E I H Y R K N K Q 1 190 E K A E IH Y R K N K Q L M R 1 204 R L Q K Q A E K N M K K K I D 1 299 T S S S TY D S L S P Y G P R 1 302 S T Y D S L S P Y G P R N P L 1 327 G G L K KP A R H C Q G Q K H 1 336 C Q G Q K H N V L A R G K P Q 1 350 Q R K P KS E N N S W Y V E N 1 353 P K S E N N S W Y V E N G R P 1 354 K S E N NS W Y V E N G R P A 1 386 L E E G L G G K Q K D K E R K 1 389 G L G G KQ K D K E R K A E N 1 399 R K A E N G P H L L V E A E Q 1

[0849] TABLE XLIX SEQ. ID Pos 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 score NO.151P3D4 v.1: HLA Peptide Scoring Results DRB1*0301 15 - mers SYFPEITHI149 T V V V A L D L Q G V V F P Y 28 333 R F V G F P D K K H K L Y G V27 261 F Y Y L I H P T K L T Y D E A 26 161 F P Y F P R L G R Y N L N FH 24 171 N L N F H E A Q Q A C L D Q D 24 191 F D Q L Y D A W R G G L DW C 24 229 Q N T V P G V R N Y G F W D K 24 250 V F C F T S N F N G R FY Y L 24 122 A S L V I T D L T L E D Y G R 23 206 N A G W L S D G S V QY P I T 23 267 P T K L T Y D E A V Q A C L N 23 81 W T K L T S D Y L K EV D V F 22 237 N Y G F W D K D K S R Y D V F 22 305 D A G W L A D G S VR Y P I S 22 38 P H L L V E A E Q A K V F S H 21 113 F L K G G S D S D AS L V I T 21 142 I E G L E D D T V V V A L D L 21 179 Q A C L D Q D A VI A S F D Q 21 184 Q D A V I A S F D Q L Y D A W 21 296 W K I L G Y D RC D A G W L A 21 21 N Y T L D H D R A I H I Q A E 20 37 G P H L L V E AE Q A K V F S 20 60 P C K F Y R D P T A F G S G I 20 126 I T D L T L E DY G R Y K C E 20 123 S L V I T D L T L E D Y G R Y 19 138 K C E V I E GL E D D T V V V 19 156 L Q G V V F P Y F P R L G R Y 19 7 L V L I S I CW A D H L S D N 18 29 A I H I Q A E N G P H L L V E 18 39 H L L V E A EQ A K V F S H R 18 54 G G N V T L P C K F Y R D P T 18 89 L K E V D V FV S M G Y H K K 18 128 D L T L E D Y G R Y K C E V I 18 153 A L D L Q GV V F P Y F P R L 18 163 Y F P R L G R Y N L N F H E A 18 185 D A V I AS F D Q L Y D A W R 18 199 R G G L D W C N A G W L S D G 18 290 G Q I FA A W K I L G Y D R C 18 295 A W K I L G Y D R C D A G W L 18 334 F V GF P D K K H K L Y G V Y 18 27 D R A I H I Q A E N G P H L L 17 95 F V SM G Y H K K T Y G G Y Q 17 216 Q Y P I T K P R E P C G G Q N 17 273 D EA V Q A C L N D G A Q I A 17 277 Q A C L N D G A Q I A K V G Q 17 283 GA Q I A K V G Q I F A A W K 17 289 V G Q I F A A W K I L G Y D R 17 48 KV F S H R G G N V T L P C K 16 103 K T Y G G Y Q G R V F L K G G 16 158G V V F P Y F P R L G R Y N L 16 248 Y D V F C F T S N F N G R F Y 16269 K L T Y D E A V Q A C L N D G 16 315 R Y P I S R P R R R C S P T E16 332 V R F V G F P D K K H K L Y G 16 13 C W A D H L S D N Y T L D H D15 252 C F T S N F N G R F Y Y L I H 15 2 K S L L L L V L I S I C W A D14 14 W A D H L S D N Y T L D H D R 14 94 V F V S M G Y H K K T Y G G Y14 141 V I E G L E D D T V V V A L D 14 276 V Q A C L N D G A Q I A K VG 14 1 M K S L L L L V L I S I C W A 13 4 L L L L V L I S I C W A D H L13 5 L L L V L I S I C W A D H L S 13 6 L L V L I S I C W A D H L S D 1319 S D N Y T L D H D R A I H I Q 13 127 T D L T L E D Y G R Y K C E V 13147 D D T V V V A L D L Q G V V F 13 151 V V A L D L Q G V V F P Y F P13 197 A W R G G L D W C N A G W L S 13 3 S L L L L V L I S I C W A D H12 46 Q A K V F S H R G G N V T L P 12 74 I H K I R I K W T K L T S D Y12 76 K I R I K W T K L T S D Y L K 12 86 S D Y L K E V D V F V S M G Y12 92 V D V F V S M G Y H K K T Y G 12 93 D V F V S M G Y H K K T Y G G12 109 Q G R V F L K G G S D S D A S 12 111 R V F L K G G S D S D A S LV 12 115 K G G S D S D A S L V I T D L 12 121 D A S L V I T D L T L E DY G 12 148 D T V V V A L D L Q G V V F P 12 157 Q G V V F P Y F P R L GR Y N 12 169 R Y N L N F H E A Q Q A C L D 12 177 A Q Q A C L D Q D A VI A S F 12 190 S F D Q L Y D A W R G G L D W 12 207 A G W L S D G S V QY P I T K 12 232 V P G V R N Y G F W D K D K S 12 262 Y Y L I H P T K LT Y D E A V 12 299 L G Y D R C D A G W L A D G S 12 329 E A A V R F V GF P D K K H K 12 9 L I S I C W A D H L S D N Y T 11 15 A D H L S D N Y TL D H D R A 11 30 I H I Q A E N G P H L L V E A 11 73 G I H K I R I K WT K L T S D 11 87 D Y L K E V D V F V S M G Y H 11 110 G R V F L K G G SD S D A S L 11 120 S D A S L V I T D L T L E D Y 11 139 C E V I E G L ED D T V V V A 11 150 V V V A L D L Q G V V F P Y F 11 164 F P R L G R YN L N F H E A Q 11 227 G G Q N T V P G V R N Y G F W 11 236 R N Y G F WD K D K S R Y D V 11 238 Y G F W D K D K S R Y D V F C 11 243 K D K S RY D V F C F T S N F 11 247 R Y D V F C F T S N F N G R F 11 286 I A K VG Q I F A A W K I L G 11 306 A G W L A D G S V R Y P I S R 11 311 D G SV R Y P I S R P R R R C 11 331 A V R F V G F P D K K H K L Y 11 339 D KK H K L Y G V Y C F R A Y 11 10 I S I C W A D H L S D N Y T L 10 11 S IC W A D H L S D N Y T L D 10 47 A K V F S H R G G N V T L P C 10 52 H RG G N V T L P C K F Y R D 10 53 R G G N V T L P C K F Y R D P 10 56 N VT L P C K F Y R D P T A F 10 71 G S G I H K I R I K W T K L T 10 84 L TS D Y L K E V D V F V S M 10 91 E V D V F V S M G Y H K K T Y 10 143 E GL E D D T V V V A L D L Q 10 145 L E D D T V V V A L D L Q G V 10 152 VA L D L Q G V V F P Y F P R 10 183 D Q D A V I A S F D Q L Y D A 10 186A V I A S F D Q L Y D A W R G 10 212 D G S V Q Y P I T K P R E P C 10246 S R Y D V F C F T S N F N G R 10 259 G R F Y Y L I H P T K L T Y D10 282 D G A Q I A K V G Q I F A A W 10 337 F P D K K H K L Y G V Y C FR 10 20 D N Y T L D H D R A I H I Q A 9 59 L P C K F Y R D P T A F G S G9 67 P T A F G S G I H K I R I K W 9 77 I R I K W T K L T S D Y L K E 978 R I K W T K L T S D Y L K E V 9 118 S D S D A S L V I T D L T L E 9134 Y G R Y K C E V I E G L E D D 9 168 G R Y N L N F H E A Q Q A C L 9180 A C L D Q D A V I A S F D Q L 9 188 I A S F D Q L Y D A W R G G L 9198 W R G G L D W C N A G W L S D 9 228 G Q N T V P G V R N Y G F W D 9254 T S N F N G R F Y Y L I H P T 9 266 H P T K L T Y D E A V Q A C L 9288 K V G Q I F A A W K I L G Y D 9 314 V R Y P I S R P R R R C S P T 9321 P R R R C S P T E A A V R F V 9 323 R R C S P T E A A V R F V G F 9326 S P T E A A V R F V G F P D K 9 28 R A I H I Q A E N G P H L L V 835 E N G P H L L V E A E Q A K V 8 40 L L V E A E Q A K V F S H R G 8 70F G S G I H K I R I K W T K L 8 75 H K I R I K W T K L T S D Y L 8 83 KL T S D Y L K E V D V F V S 8 97 S M G Y H K K T Y G G Y Q G R 8 102 K KT Y G G Y Q G R V F L K G 8 107 G Y Q G R V F L K G G S D S D 8 124 L VI T D L T L E D Y G R Y K 8 132 E D Y G R Y K C E V I E G L E 8 135 G RY K C E V I E G L E D D T 8 159 V V F P Y F P R L G R Y N L N 8 165 P RL G R Y N L N F H E A Q Q 8 170 Y N L N F H E A Q Q A C L D Q 8 215 V QY P I T K P R E P C G G Q 8 221 K P R E P C G G Q N T V P G V 8 239 G FW D K D K S R Y D V F C F 8 240 F W D K D K S R Y D V F C F T 8 242 D KD K S R Y D V F C F T S N 8 251 F C F T S N F N G R F Y Y L I 8 253 F TS N F N G R F Y Y L I H P 8 258 N G R F Y Y L I H P T K L T Y 8 298 I LG Y D R C D A G W L A D G 8 312 G S V R Y P I S R P R R R C S 8 316 Y PI S R P R R R C S P T E A 8 25 D H D R A I H I Q A E N G P H 7 45 E Q AK V F S H R G G N V T L 7 72 S G I H K I R I K W T K L T S 7 82 T K L TS D Y L K E V D V F V 7 176 E A Q Q A C L D Q D A V I A S 7 213 G S V QY P I T K P R E P C G 7 235 V R N Y G F W D K D K S R Y D 7 280 L N D GA Q I A K V G Q I F A 7 335 V G F P D K K H K L Y G V Y C 7 57 V T L P CK F Y R D P T A F G 6 68 T A F G S G I H K I R I K W T 6 101 H K K T Y GG Y Q G R V F L K 6 130 T L E D Y G R Y K C E V I E G 6 208 G W L S D GS V Q Y P I T K P 6 222 P R E P C G G Q N T V P G V R 6 307 G W L A D GS V R Y P I S R P 6 325 C S P T E A A V R F V G F P D 6 36 N G P H L L VE A E Q A K V F 4 55 G N V T L P C K F Y R D P T A 4 79 I K W T K L T SD Y L K E V D 4 80 K W T K L T S D Y L K E V D V 4 162 P Y F P R L G R YN L N F H E 4 220 T K P R E P C G G Q N T V P G 4 260 R F Y Y L I H P TK L T Y D E 4 24 L D H D R A I H I Q A E N G P 3 31 H I Q A E N G P H LL V E A E 3 33 Q A E N G P H L L V E A E Q A 3 85 T S D Y L K E V D V FV S M G 3 100 Y H K K T Y G G Y Q G R V F L 3 125 V I T D L T L E D Y GR Y K C 3 178 Q Q A C L D Q D A V I A S F D 3 211 S D G S V Q Y P I T KP R E P 3 217 Y P I T K P R E P C G G Q N T 3 241 W D K D K S R Y D V FC F T S 3 265 I H P T K L T Y D E A V Q A C 3 285 Q I A K V G Q I F A AW K I L 3 300 G Y D R C D A G W L A D G S V 3 320 R P R R R C S P T E AA V R F 3 322 R R R C S P T E A A V R F V G 3 8 V L I S I C W A D H L SD N Y 2 12 I C W A D H L S D N Y T L D H 2 26 H D R A I H I Q A E N G PH L 2 34 A E N G P H L L V E A E Q A K 2 44 A E Q A K V F S H R G G N VT 2 49 V F S H R G G N V T L P C K F 2 64 Y R D P T A F G S G I H K I R2 66 D P T A F G S G I H K I R I K 2 90 K E V D V F V S M G Y H K K T 299 G Y H K K T Y G G Y Q G R V F 2 105 Y G G Y Q G R V F L K G G S D 2108 Y Q G R V F L K G G S D S D A 2 116 G G S D S D A S L V I T D L T 2119 D S D A S L V I T D L T L E D 2 136 R Y K C E V I E G L E D D T V 2137 Y K C E V I E G L E D D T V V 2 144 G L E D D T V V V A L D L Q G 2146 E D D T V V V A L D L Q G V V 2 155 D L Q G V V F P Y F P R L G R 2160 V F P Y F P R L G R Y N L N F 2 167 L G R Y N L N F H E A Q Q A C 2175 H E A Q Q A C L D Q D A V I A 2 187 V I A S F D Q L Y D A W R G G 2193 Q L Y D A W R G G L D W C N A 2 195 Y D A W R G G L D W C N A G W 2201 G L D W C N A G W L S D G S V 2 219 I T K P R E P C G G Q N T V P 2226 C G G Q N T V P G V R N Y G F 2 268 T K L T Y D E A V Q A C L N D 2271 T Y D E A V Q A C L N D G A Q 2 272 Y D E A V Q A C L N D G A Q I 2275 A V Q A C L N D G A Q I A K V 2 278 A C L N D G A Q I A K V G Q I 2284 A Q I A K V G Q I F A A W K I 2 293 F A A W K I L G Y D R C D A G 2294 A A W K I L G Y D R C D A G W 2 310 A D G S V R Y P I S R P R R R 2319 S R P R R R C S P T E A A V R 2 324 R C S P T E A A V R F V G F P 2336 G F P D K K H K L Y G V Y C F 2 340 K K H K L Y G V Y C F R A Y N 217 H L S D N Y T L D H D R A I H 1 32 I Q A E N G P H L L V E A E Q 1 41L V E A E Q A K V F S H R G G 1 50 F S H R G G N V T L P C K F Y 1 58 TL P C K F Y R D P T A F G S 1 61 C K F Y R D P T A F G S G I H 1 62 K FY R D P T A F G S G I H K 1 65 R D P T A F G S G I H K I R I 1 69 A F GS G I H K I R I K W T K 1 88 Y L K E V D V F V S M G Y H K 1 96 V S M GY H K K T Y G G Y Q G 1 98 M G Y H K K T Y G G Y Q G R V 1 104 T Y G G YQ G R V F L K G G S 1 112 V F L K G G S D S D A S L V I 1 114 L K G G SD S D A S L V I T D 1 117 G S D S D A S L V I T D L T L 1 131 L E D Y GR Y K C E V I E G L 1 133 D Y G R Y K C E V I E G L E D 1 140 E V I E GL E D D T V V V A L 1 172 L N F H E A Q Q A C L D Q D A 1 173 N F H E AQ Q A C L D Q D A V 1 189 A S F D Q L Y D A W R G G L D 1 192 D Q L Y DA W R G G L D W C N 1 194 L Y D A W R G G L D W C N A G 1 196 D A W R GG L D W C N A G W L 1 200 G G L D W C N A G W L S D G S 1 203 D W C N AG W L S D G S V Q Y 1 204 W C N A G W L S D G S V Q Y P 1 205 C N A G WL S D G S V Q Y P I 1 209 W L S D G S V Q Y P I T K P R 1 214 S V Q Y PI T K P R E P C G G 1 218 P I T K P R E P C G G Q N T V 1 223 R E P C GG Q N T V P G V R N 1 231 T V P G V R N Y G F W D K D K 1 233 P G V R NY G F W D K D K S R 1 249 D V F C F T S N F N G R F Y Y 1 255 S N F N GR F Y Y L I H P T K 1 256 N F N G R F Y Y L I H P T K L 1 257 F N G R FY Y L I H P T K L T 1 263 Y L I H P T K L T Y D E A V Q 1 264 L I H P TK L T Y D E A V Q A 1 270 L T Y D E A V Q A C L N D G A 1 274 E A V Q AC L N D G A Q I A K 1 281 N D G A Q I A K V G Q I F A A 1 287 A K V G QI F A A W K I L G Y 1 292 I F A A W K I L G Y D R C D A 1 297 K I L G YD R C D A G W L A D 1 301 Y D R C D A G W L A D G S V R 1 302 D R C D AG W L A D G S V R Y 1 304 C D A G W L A D G S V R Y P I 1 308 W L A D GS V R Y P I S R P R 1 318 I S R P R R R C S P T E A A V 1 328 T E A A VR F V G F P D K K H 1 330 A A V R F V G F P D K K H K L 1 338 P D K K HK L Y G V Y C F R A 1 151P3D4 v.2: HLA Peptide Scoring Results DRB1*030115 - mers SYFPEITHI 26 G Q K M K Q D K K V D L L V P 37 73 H W T V Y Q DE K Q R K D K V 28 56 H V Q F V G S Y K L A Y S N D 25 191 K A E I H Y RK N K Q L M R L 25 43 V T G I I T Q G A K D F G H V 20 54 F G H V Q F VG S Y K L A Y S 20 84 K D K V L L G R K A V V V S C 20 200 K Q L M R L QK Q A E K N M K 20 299 T S S S T Y D S L S P Y G P R 20 34 K V D L L V PT K V T G I I T 19 177 Y Q A V T A T L E E K R K E K 19 340 K H N V L AR G K P Q R K P K 19 359 S W Y V E N G R P A D L A G S 19 380 W K A I ES L E E G L G G K Q 19 14 L H I V V E S I R D H S G Q K 18 181 T A T L EE K R K E K A E I H 18 199 N K Q L M R L Q K Q A E K N M 18 231 G L G FI F K T I A P L A A T 18 390 L G G K Q K D K E R K A E N G 18 44 T G I IT Q G A K D F G H V Q 17 64 K L A Y S N D G E H W T V Y Q 17 91 R K A VV V S C E G I N I S G 17 101 I N I S G S F C R N K L K Y L 17 104 S G SF C R N K L K Y L A F L 17 115 L A F L H K R M N T N P S R R 17 136 P SR I F W R Q E K A D G G S 17 170 P H E V G W K Y Q A V T A T L 17 202 LM R L Q K Q A E K N M K K K 17 326 G G G L K K P A R H C Q G Q K 17 376C G A L W K A I E S L E E G L 17 379 L W K A I E S L E E G L G G K 17387 E E G L G G K Q K D K E R K A 17 11 L R A L H I V V E S I R D H S 1678 Q D E K Q R K D K V L L G R K 16 103 I S G S F C R N K L K Y L A F 16112 L K Y L A F L H K R M N T N P 16 120 K R M N T N P S R R P Y H F Q16 137 S R I F W R Q E K A D G G S C 16 155 G H A S E A Y K K V C L S GA 16 185 E E K R K E K A E I H Y R K N 16 214 K K K I D K Y T E S P G GG S 16 229 P R G L G F I F K T I A P L A 16 305 D S L S P Y G P R N P LP N P 16 350 Q R K P K S E N N S W Y V E N 16 130 P Y H F Q V P S R I FW R Q E 15 18 V E S I R D H S G Q K M K Q D 14 79 D E K Q R K D K V L LG R K A 14 85 D K V L L G R K A V V V S C E 14 92 K A V V V S C E G I NI S G S 14 30 K Q D K K V D L L V P T K V T 13 35 V D L L V P T K V T GI I T Q 13 57 V Q F V G S Y K L A Y S N D G 13 273 R A P V P A A S P A AW L P L 13 304 Y D S L S P Y G P R N P L P N 13 383 I E S L E E G L G GK Q K D K 13 8 T F P L R A L H I V V E S I R 12 13 A L H I V V E S I R DH S G Q 12 32 D K K V D L L V P T K V T G I 12 40 P T K V T G I I T Q GA K D F 12 93 A V V V S C E G I N I S G S F 12 109 R N K L K Y L A F L HK R M N 12 141 W R Q E K A D G G S C C P Q G 12 161 Y K K V C L S G A PH E V G W 12 212 N M K K K I D K Y T E S P G G 12 341 H N V L A R G K PQ R K P K S 12 3 E H T T K T F P L R A L H I V 11 15 H I V V E S I R D HS G Q K M 11 17 V V E S I R D H S G Q K M K Q 11 48 T Q G A K D F G H VQ F V G S 11 86 K V L L G R K A V V V S C E G 11 98 C E G I N I S G S FC R N K L 11 100 G I N I S G S F C R N K L K Y 11 106 S F C R N K L K YL A F L H K 11 107 F C R N K L K Y L A F L H K R 11 114 Y L A F L H K RM N T N P S R 11 119 H K R M N T N P S R R P Y H F 11 132 H F Q V P S RI F W R Q E K A 11 163 K V C L S G A P H E V G W K Y 11 210 E K N M K KK I D K Y T E S P 11 232 L G F I F K T I A P L A A T R 11 233 G F I F KT I A P L A A T R A 11 236 F K T I A P L A A T R A T R I 11 247 A T R IG H P G G R T P R A G 11 267 P P A L S A R A P V P A A S P 11 282 A A WL P L R T P W T R P S S 11 284 W L P L R T P W T R P S S C P 11 348 K PQ R K P K S E N N S W Y V 11 363 E N G R P A D L A G S G Y C G 11 367 PA D L A G S G Y C G A L W K 11 397 K E R K A E N G P H L L V E A 11 4 HT T K T F P L R A L H I V V 10 27 Q K M K Q D K K V D L L V P T 10 36 DL L V P T K V T G I I T Q G 10 47 I T Q G A K D F G H V Q F V G 10 62 SY K L A Y S N D G E H W T V 10 77 Y Q D E K Q R K D K V L L G R 10 83 RK D K V L L G R K A V V V S 10 179 A V T A T L E E K R K E K A E 10 180V T A T L E E K R K E K A E I 10 198 K N K Q L M R L Q K Q A E K N 10209 A E K N M K K K I D K Y T E S 10 223 S P G G G S P R G L G F I F K10 239 I A P L A A T R A T R I G H P 10 274 A P V P A A S P A A W L P LR 10 276 V P A A S P A A W L P L R T P 10 293 R P S S C P T S S S T Y DS L 10 312 P R N P L P N P R H S P S G G 10 313 R N P L P N P R H S P SG G G 10 318 N P R H S P S G G G G L K K P 10 333 A R H C Q G Q K H N VL A R G 10 358 N S W Y V E N G R P A D L A G 10 368 A D L A G S G Y C GA L W K A 10 375 Y C G A L W K A I E S L E E G 10 385 S L E E G L G G KQ K D K E R 10 6 T K T F P L R A L H I V V E S 9 51 A K D F G H V Q F VG S Y K L 9 61 G S Y K L A Y S N D G E H W T 9 105 G S F C R N K L K Y LA F L H 9 113 K Y L A F L H K R M N T N P S 9 122 M N T N P S R R P Y HF Q V P 9 129 R P Y H F Q V P S R I F W R Q 9 150 S C C P Q G H A S E AY K K V 9 166 L S G A P H E V G W K Y Q A V 9 173 V G W K Y Q A V T A TL E E K 9 183 T L E E K R K E K A E I H Y R 9 190 E K A E I H Y R K N KQ L M R 9 193 E I H Y R K N K Q L M R L Q K 9 194 I H Y R K N K Q L M RL Q K Q 9 203 M R L Q K Q A E K N M K K K I 9 221 T E S P G G G S P R GL G F I 9 225 G G G S P R G L G F I F K T I 9 238 T I A P L A A T R A TR I G H 9 259 R A G S S A H R P P A L S A R 9 296 S C P T S S S T Y D SL S P Y 9 342 N V L A R G K P Q R K P K S E 9 344 L A R G K P Q R K P KS E N N 9 386 L E E G L G G K Q K D K E R K 9 391 G G K Q K D K E R K AE N G P 9 396 D K E R K A E N G P H L L V E 9 20 S I R D H S G Q K M K QD K K 8 23 D H S G Q K M K Q D K K V D L 8 52 K D F G H V Q F V G S Y KL A 8 66 A Y S N D G E H W T V Y Q D E 8 74 W T V Y Q D E K Q R K D K VL 8 96 V S C E G I N I S G S F C R N 8 117 F L H K R M N T N P S R R P Y8 134 Q V P S R I F W R Q E K A D G 8 135 V P S R I F W R Q E K A D G G8 151 C C P Q G H A S E A Y K K V C 8 182 A T L E E K R K E K A E I H Y8 192 A E I H Y R K N K Q L M R L Q 8 196 Y R K N K Q L M R L Q K Q A E8 204 R L Q K Q A E K N M K K K I D 8 207 K Q A E K N M K K K I D K Y T8 208 Q A E K N M K K K I D K Y T E 8 222 E S P G G G S P R G L G F I F8 248 T R I G H P G G R T P R A G S 8 251 G H P G G R T P R A G S S A H8 265 H R P P A L S A R A P V P A A 8 280 S P A A W L P L R T P W T R P8 285 L P L R T P W T R P S S C P T 8 310 Y G P R N P L P N P R H S P S8 323 P S G G G G L K K P A R H C Q 8 334 R H C Q G Q K H N V L A R G K8 349 P Q R K P K S E N N S W Y V E 8 364 N G R P A D L A G S G Y C G A8 395 K D K E R K A E N G P H L L V 8 19 E S I R D H S G Q K M K Q D K 722 R D H S G Q K M K Q D K K V D 7 41 T K V T G I I T Q G A K D F G 7 72E H W T V Y Q D E K Q R K D K 7 75 T V Y Q D E K Q R K D K V L L 7 76 VY Q D E K Q R K D K V L L G 7 94 V V V S C E G I N I S G S F C 7 102 N IS G S F C R N K L K Y L A 7 121 R M N T N P S R R P Y H F Q V 7 126 P SR R P Y H F Q V P S R I F 7 146 A D G G S C C P Q G H A S E A 7 154 Q GH A S E A Y K K V C L S G 7 164 V C L S G A P H E V G W K Y Q 7 178 Q AV T A T L E E K R K E K A 7 189 K E K A E I H Y R K N K Q L M 7 206 Q KQ A E K N M K K K I D K Y 7 211 K N M K K K I D K Y T E S P G 7 241 P LA A T R A T R I G H P G G 7 258 P R A G S S A H R P P A L S A 7 306 S LS P Y G P R N P L P N P R 7 322 S P S G G G G L K K P A R H C 7 331 K PA R H C Q G Q K H N V L A 7 332 P A R H C Q G Q K H N V L A R 7 338 G QK H N V L A R G K P Q R K 7 346 R G K P Q R K P K S E N N S W 7 355 S EN N S W Y V E N G R P A D 7 356 E N N S W Y V E N G R P A D L 7 373 S GY C G A L W K A I E S L E 7 389 G L G G K Q K D K E R K A E N 7 392 G KQ K D K E R K A E N G P H 7 394 Q K D K E R K A E N G P H L L 7 25 S G QK M K Q D K K V D L L V 6 50 G A K D F G H V Q F V G S Y K 6 70 D G E HW T V Y Q D E K Q R K 6 168 G A P H E V G W K Y Q A V T A 6 329 L K K PA R H C Q G Q K H N V 6 343 V L A R G K P Q R K P K S E N 6 33 K K V D LL V P T K V T G I I 4 108 C R N K L K Y L A F L H K R M 4 169 A P H E VG W K Y Q A V T A T 4 234 F I F K T I A P L A A T R A T 4 382 A I E S LE E G L G G K Q K D 4 393 K Q K D K E R K A E N G P H L 4 7 K T F P L RA L H I V V E S I 3 24 H S G Q K M K Q D K K V D L L 3 42 K V T G I I TQ G A K D F G H 3 60 V G S Y K L A Y S N D G E H W 3 82 Q R K D K V L LG R K A V V V 3 99 E G I N I S G S F C R N K L K 3 111 K L K Y L A F L HK R M N T N 3 125 N P S R R P Y H F Q V P S R I 3 148 G G S C C P Q G HA S E A Y K 3 159 E A Y K K V C L S G A P H E V 3 160 A Y K K V C L S GA P H E V G 3 162 K K V C L S G A P H E V G W K 3 197 R K N K Q L M R LQ K Q A E K 3 201 Q L M R L Q K Q A E K N M K K 3 217 I D K Y T E S P GG G S P R G 3 235 I F K T I A P L A A T R A T R 3 255 G R T P R A G S SA H R P P A 3 260 A G S S A H R P P A L S A R A 3 262 S S A H R P P A LS A R A P V 3 263 S A H R P P A L S A R A P V P 3 266 R P P A L S A R AP V P A A S 3 269 A L S A R A P V P A A S P A A 3 270 L S A R A P V P AA S P A A W 3 272 A R A P V P A A S P A A W L P 3 281 P A A W L P L R TP W T R P S 3 283 A W L P L R T P W T R P S S C 3 289 T P W T R P S S CP T S S S T 3 295 S S C P T S S S T Y D S L S P 3 303 T Y D S L S P Y GP R N P L P 3 309 P Y G P R N P L P N P R H S P 3 319 P R H S P S G G GG L K K P A 3 320 R H S P S G G G G L K K P A R 3 324 S G G G G L K K PA R H C Q G 3 325 G G G G L K K P A R H C Q G Q 3 330 K K P A R H C Q GQ K H N V L 3 347 G K P Q R K P K S E N N S W Y 3 362 V E N G R P A D LA G S G Y C 3 366 R P A D L A G S G Y C G A L W 3 377 G A L W K A I E SL E E G L G 3 381 K A I E S L E E G L G G K Q K 3 398 E R K A E N G P HL L V E A E 3 400 K A E N G P H L L V E A E Q A 3 1 M L E H T T K T F PL R A L H 2 2 L E H T T K T F P L R A L H I 2 5 T T K T F P L R A L H IV V E 2 9 F P L R A L H I V V E S I R D 2 10 P L R A L H I V V E S I R DH 2 12 R A L H I V V E S I R D H S G 2 28 K M K Q D K K V D L L V P T K2 29 M K Q D K K V D L L V P T K V 2 31 Q D K K V D L L V P T K V T G 238 L V P T K V T G I I T Q G A K 2 55 G H V Q F V G S Y K L A Y S N 2 67Y S N D G E H W T V Y Q D E K 2 71 G E H W T V Y Q D E K Q R K D 2 80 EK Q R K D K V L L G R K A V 2 87 V L L G R K A V V V S C E G I 2 90 G RK A V V V S C E G I N I S 2 97 S C E G I N I S G S F C R N K 2 110 N K LK Y L A F L H K R M N T 2 116 A F L H K R M N T N P S R R P 2 131 Y H FQ V P S R I F W R Q E K 2 138 R I F W R Q E K A D G G S C C 2 145 K A DG G S C C P Q G H A S E 2 152 C P Q G H A S E A Y K K V C L 2 153 P Q GH A S E A Y K K V C L S 2 156 H A S E A Y K K V C L S G A P 2 165 C L SG A P H E V G W K Y Q A 2 167 S G A P H E V G W K Y Q A V T 2 172 E V GW K Y Q A V T A T L E E 2 184 L E E K R K E K A E I H Y R K 2 188 R K EK A E I H Y R K N K Q L 2 195 H Y R K N K Q L M R L Q K Q A 2 205 L Q KQ A E K N M K K K I D K 2 215 K K I D K Y T E S P G G G S P 2 218 D K YT E S P G G G S P R G L 2 219 K Y T E S P G G G S P R G L G 2 224 P G GG S P R G L G F I F K T 2 226 G G S P R G L G F I F K T I A 2 227 G S PR G L G F I F K T I A P 2 228 S P R G L G F I F K T I A P L 2 230 R G LG F I F K T I A P L A A 2 237 K T I A P L A A T R A T R I G 2 244 A T RA T R I G H P G G R T P 2 246 R A T R I G H P G G R T P R A 2 253 P G GR T P R A G S S A H R P 2 254 G G R T P R A G S S A H R P P 2 261 G S SA H R P P A L S A R A P 2 264 A H R P P A L S A R A P V P A 2 268 P A LS A R A P V P A A S P A 2 275 P V P A A S P A A W L P L R T 2 278 A A SP A A W L P L R T P W T 2 288 R T P W T R P S S C P T S S S 2 291 W T RP S S C P T S S S T Y D 2 297 C P T S S S T Y D S L S P Y G 2 301 S S TY D S L S P Y G P R N P 2 302 S T Y D S L S P Y G P R N P L 2 307 L S PY G P R N P L P N P R H 2 308 S P Y G P R N P L P N P R H S 2 316 L P NP R H S P S G G G G L K 2 317 P N P R H S P S G G G G L K K 2 321 H S PS G G G G L K K P A R H 2 327 G G L K K P A R H C Q G Q K H 2 335 H C QG Q K H N V L A R G K P 2 336 C Q G Q K H N V L A R G K P Q 2 339 Q K HN V L A R G K P Q R K P 2 354 K S E N N S W Y V E N G R P A 2 360 W Y VE N G R P A D L A G S G 2 361 Y V E N G R P A D L A G S G Y 2 365 G R PA D L A G S G Y C G A L 2 369 D L A G S G Y C G A L W K A I 2 370 L A GS G Y C G A L W K A I E 2 372 G S G Y C G A L W K A I E S L 2 374 G Y CG A L W K A I E S L E E 2 21 I R D H S G Q K M K Q D K K V 1 37 L L V PT K V T G I I T Q G A 1 39 V P T K V T G I I T Q G A K D 1 45 G I I T QG A K D F G H V Q F 1 49 Q G A K D F G H V Q F V G S Y 1 53 D F G H V QF V G S Y K L A Y 1 58 Q F V G S Y K L A Y S N D G E 1 59 F V G S Y K LA Y S N D G E H 1 63 Y K L A Y S N D G E H W T V Y 1 65 L A Y S N D G EH W T V Y Q D 1 69 N D G E H W T V Y Q D E K Q R 1 81 K Q R K D K V L LG R K A V V 1 88 L L G R K A V V V S C E G I N 1 123 N T N P S R R P Y HF Q V P S 1 124 T N P S R R P Y H F Q V P S R 1 139 I F W R Q E K A D GG S C C P 1 142 R Q E K A D G G S C C P Q G H 1 143 Q E K A D G G S C CP Q G H A 1 147 D G G S C C P Q G H A S E A Y 1 157 A S E A Y K K V C LS G A P H 1 158 S E A Y K K V C L S G A P H E 1 171 H E V G W K Y Q A VT A T L E 1 174 G W K Y Q A V T A T L E E K R 1 175 W K Y Q A V T A T LE E K R K 1 176 K Y Q A V T A T L E E K R K E 1 186 E K R K E K A E I HY R K N K 1 187 K R K E K A E I H Y R K N K Q 1 213 M K K K I D K Y T ES P G G G 1 216 K I D K Y T E S P G G G S P R 1 220 Y T E S P G G G S PR G L G F 1 242 L A A T R A T R I G H P G G R 1 245 T R A T R I G H P GG R T P R 1 250 I G H P G G R T P R A G S S A 1 252 H P G G R T P R A GS S A H R 1 256 R T P R A G S S A H R P P A L 1 257 T P R A G S S A H RP P A L S 1 277 P A A S P A A W L P L R T P W 1 279 A S P A A W L P L RT P W T R 1 287 L R T P W T R P S S C P T S S 1 290 P W T R P S S C P TS S S T Y 1 294 P S S C P T S S S T Y D S L S 1 298 P T S S S T Y D S LS P Y G P 1 300 S S S T Y D S L S P Y G P R N 1 311 G P R N P L P N P RH S P S G 1 314 N P L P N P R H S P S G G G G 1 315 P L P N P R H S P SG G G G L 1 328 G L K K P A R H C Q G Q K H N 1 337 Q G Q K H N V L A RG K P Q R 1 345 A R G K P Q R K P K S E N N S 1 351 R K P K S E N N S WY V E N G 1 352 K P K S E N N S W Y V E N G R 1 353 P K S E N N S W Y VE N G R P 1 371 A G S G Y C G A L W K A I E S 1 378 A L W K A I E S L EE G L G G 1 384 E S L E E G L G G K Q K D K E 1 388 E G L G G K Q K D KE R K A E 1 399 R K A E N G P H L L V E A E Q 1

[0850] TABLE L SEQ. ID Pos 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 score NO.151P3D4 v.1: HLA Peptide Scoring Results DRB1*0401 15-mers SYFPEITHI 78R I K W T K L T S D Y L K E V 28 161 F P Y F P R L G R Y N L N F H 28171 N L N F H E A Q Q A C L D Q D 28 258 N G R F Y Y L I H P T K L T Y28 269 K L T Y D E A V Q A C L N D G 28 38 P H L L V E A E Q A K V F S H26 149 T V V V A L D L Q G V V F P Y 26 191 F D Q L Y D A W R G G L D WC 26 247 R Y D V F C F T S N F N G R F 26 283 G A Q I A K V G Q I F A AW K 26 19 S D N Y T L D H D R A I H I Q 22 60 P C K F Y R D P T A F G SG I 22 85 T S D Y L K E V D V F V S M G 22 134 Y G R Y K C E V I E G L ED D 22 158 G V V F P Y F P R L G R Y N L 22 167 L G R Y N L N F H E A QQ A C 22 206 N A G W L S D G S V Q Y P I T 22 238 Y G F W D K D K S R YD V F C 22 245 K S R Y D V F C F T S N F N G 22 259 G R F Y Y L I H P TK L T Y D 22 260 R F Y Y L I H P T K L T Y D E 22 305 D A G W L A D G SV R Y P I S 22 1 M K S L L L L V L I S I C W A 20 3 S L L L L V L I S IC W A D H 20 4 L L L L V L I S I C W A D H L 20 9 L I S I C W A D H L SD N Y T 20 21 N Y T L D H D R A I H I Q A E 20 29 A I H I Q A E N G P HL L V E 20 37 G P H L L V E A E Q A K V F S 20 71 G S G I H K I R I K WT K L T 20 81 W T K L T S D Y L K E V D V F 20 86 S D Y L K E V D V F VS M G Y 20 89 L K E V D V F V S M G Y H K K 20 93 D V F V S M G Y H K KT Y G G 20 122 A S L V I T D L T L E D Y G R 20 139 C E V I E G L E D DT V V V A 20 142 I E G L E D D T V V V A L D L 20 148 D T V V V A L D LQ G V V F P 20 179 Q A C L D Q D A V I A S F D Q 20 185 D A V I A S F DQ L Y D A W R 20 229 Q N T V P G V R N Y G F W D K 20 267 P T K L T Y DE A V Q A C L N 20 273 D E A V Q A C L N D G A Q I A 20 111 Q A C L N DG A Q I A K V G Q 20 286 I A K V G Q I F A A W K I L G 20 295 A W K I LG Y D R C D A G W L 20 315 R Y P I S R P R R R C S P T E 20 329 E A A VR F V G F P D K K H K 20 18 L S D N Y T L D H D R A I H I 18 23 T L D HD R A I H I Q A E N G 18 57 V T L P C K F Y R D P T A F G 18 115 K G G SD S D A S L V I T D L 18 119 D S D A S L V I T D L T L E D 18 141 V I EG L E D D T V V V A L D 18 176 E A Q Q A C L D Q D A V I A S 18 182 L DQ D A V I A S F D Q L Y D 18 11 S I C W A D H L S D N Y T L D 16 61 C KF Y R D P T A F G S G I H 16 67 P T A F G S G I H K I R I K W 16 92 V DV F V S M G Y H K K T Y G 16 110 G R V F L K G G S D S D A S L 16 131 LE D Y G R Y K C E V I E G L 16 188 I A S F D Q L Y D A W R G G L 16 195Y D A W R G G L D W C N A G W 16 201 G L D W C N A G W L S D G S V 16235 V R N Y G F W D K D K S R Y D 16 248 Y D V F C F T S N F N G R F Y16 250 V F C F T S N F N G R F Y Y L 16 293 F A A W K I L G Y D R C D AG 16 298 I L G Y D R C D A G W L A D G 16 331 A V R F V G F P D K K H KL Y 16 74 I H K I R I K W T K L T S D Y 15 2 K S L L L L V L I S I C W AD 14 6 L L V L I S I C W A D H L S D 14 7 L V L I S I C W A D H L S D N14 15 A D H L S D N Y T L D H D R A 14 39 H L L V E A E Q A K V F S H R14 46 Q A K V F S H R G G N V T L P 14 91 E V D V F V S M G Y H K K T Y14 111 R V F L K G G S D S D A S L V 14 123 S L V I T D L T L E D Y G RY 14 126 I T D L T L E D Y G R Y K C E 14 128 D L T L E D Y G R Y K C EV I 14 138 K C E V I E G L E D D T V V V 14 147 D D T V V V A L D L Q GV V F 14 153 A L D L Q G V V F P Y F P R L 14 156 L Q G V V F P Y F P RL G R Y 14 169 R Y N L N F H E A Q Q A C L D 14 199 R G G L D W C N A GW L S D G 14 212 D G S V Q Y P I T K P R E P C 14 232 V P G V R N Y G FW D K D K S 14 289 V G Q I F A A W K I L G Y D R 14 296 W K I L G Y D RC D A G W L A 14 311 D G S V R Y P I S R P R R R C 14 332 V R F V G F PD K K H K L Y G 14 10 I S I C W A D H L S D N Y T L 12 12 I C W A D H LS D N Y T L D H 12 13 C W A D H L S D N Y T L D H D 12 25 D H D R A I HI Q A E N G P H 12 28 R A I H I Q A E N G P H L L V 12 31 H I Q A E N GP H L L V E A E 12 35 E N G P H L L V E A E Q A K V 12 36 N G P H L L VE A E Q A K V F 12 43 E A E Q A K V F S H R G G N V 12 44 A E Q A K V FS H R G G N V T 12 45 E Q A K V F S H R G G N V T L 12 48 K V F S H R GG N V T L P C K 12 51 S H R G G N V T L P C K F Y R 12 63 F Y R D P T AF G S G I H K I 12 64 Y R D P T A F G S G I H K I R 12 68 T A F G S G IH K I R I K W T 12 73 G I H K I R I K W T K L T S D 12 83 K L T S D Y LK E V D V F V S 12 87 D Y L K E V D V F V S M G Y H 12 101 H K K T Y G GY Q G R V F L K 12 103 K T Y G G Y Q G R V F L K G G 12 107 G Y Q G R VF L K G G S D S D 12 112 V F L K G G S D S D A S L V I 12 113 F L K G GS D S D A S L V I T 12 116 G G S D S D A S L V I T D L T 12 118 S D S DA S L V I T D L T L E 12 120 S D A S L V I T D L T L E D Y 12 127 T D LT L E D Y G R Y K C E V 12 140 E V I E G L E D D T V V V A L 12 145 L ED D T V V V A L D L Q G V 12 146 E D D T V V V A L D L Q G V V 12 166 RL G R Y N L N F H E A Q Q A 12 168 G R Y N L N F H E A Q Q A C L 12 170Y N L N F H E A Q Q A C L D Q 12 177 A Q Q A C L D Q D A V I A S F 12183 D Q D A V I A S F D Q L Y D A 12 186 A V I A S F D Q L Y D A W R G12 196 D A W R G G L D W C N A G W L 12 203 D W C N A G W L S D G S V QY 12 204 W C N A G W L S D G S V Q Y P 12 208 G W L S D G S V Q Y P I TK P 12 209 W L S D G S V Q Y P I T K P R 12 218 P I T K P R E P C G G QN T V 12 221 K P R E P C G G Q N T V P G V 12 226 C G G Q N T V P G V RN Y G F 12 234 G V R N Y G F W D K D K S R Y 12 243 K D K S R Y D V F CF T S N F 12 244 D K S R Y D V F C F T S N F N 12 264 L I H P T K L T YD E A V Q A 12 270 L T Y D E A V Q A C L N D G A 12 274 E A V Q A C L ND G A Q I A K 12 276 V Q A C L N D G A Q I A K V G 12 278 A C L N D G AQ I A K V G Q I 12 280 L N D G A Q I A K V G Q I F A 12 281 N D G A Q IA K V G Q I F A A 12 287 A K V G Q I F A A W K I L G Y 12 288 K V G Q IF A A W K I L G Y D 12 299 L G Y D R C D A G W L A D G S 12 303 R C D AG W L A D G S V R Y P 12 307 G W L A D G S V R Y P I S R P 12 308 W L AD G S V R Y P I S R P R 12 312 G S V R Y P I S R P R R R C S 12 320 R PR R R C S P T E A A V R F 12 324 R C S P T E A A V R F V G F P 12 325 CS P T E A A V R F V G F P D 12 333 R F V G F P D K K H K L Y G V 12 47 AK V F S H R G G N V T L P C 11 160 V F P Y F P R L G R Y N L N F 11 254T S N F N G R F Y Y L I H P T 11 334 F V G F P D K K H K L Y G V Y 11102 K K T Y G G Y Q G R V F L K G 10 192 D Q L Y D A W R G G L D W C N10 214 S V Q Y P I T K P R E P C G G 10 290 G Q I F A A W K I L G Y D RC 10 313 S V R Y P I S R P R R R C S P 10 109 Q G R V F L K G G S D S DA S 9 5 L L L V L I S I C W A D H L S 8 27 D R A I H I Q A E N G P H L L8 54 G G N V T L P C K F Y R D P T 8 76 K I R I K W T K L T S D Y L K 895 F V S M G Y H K K T Y G G Y Q 8 121 D A S L V I T D L T L E D Y G 8151 V V A L D L Q G V V F P Y F P 8 157 Q G V V F P Y F P R L G R Y N 8164 F P R L G R Y N L N F H E A Q 8 184 Q D A V I A S F D Q L Y D A W 8207 A G W L S D G S V Q Y P I T K 8 216 Q Y P I T K P R E P C G G Q N 8261 F Y Y L I H P T K L T Y D E A 8 262 Y Y L I H P T K L T Y D E A V 8306 A G W L A D G S V R Y P I S R 8 239 G F W D K D K S R Y D V F C F 78 V L I S I C W A D H L S D N Y 6 14 W A D H L S D N Y T L D H D R 6 20D N Y T L D H D R A I H I Q A 6 24 L D H D R A I H I Q A E N G P 6 26 HD R A I H I Q A E N G P H L 6 30 I H I Q A E N G P H L L V E A 6 33 Q AE N G P H L L V E A E Q A 6 34 A E N G P H L L V E A E Q A K 6 40 L L VE A E Q A K V F S H R G 6 41 L V E A E Q A K V F S H R G G 6 50 F S H RG G N V T L P C K F Y 6 53 R G G N V T L P C K F Y R D P 6 58 T L P C KF Y R D P T A F G S 6 65 R D P T A F G S G I H K I R I 6 66 D P T A F GS G I H K I R I K 6 69 A F G S G I H K I R I K W T K 6 75 H K I R I K WT K L T S D Y L 6 79 I K W T K L T S D Y L K E V D 6 88 Y L K E V D V FV S M G Y H K 6 90 K E V D V F V S M G Y H K K T 6 98 M G Y H K K T Y GG Y Q G R V 6 104 T Y G G Y Q G R V F L K G G S 6 106 G G Y Q G R V F LK G G S D S 6 108 Y Q G R V F L K G G S D S D A 6 114 L K G G S D S D AS L V I T D 6 125 V I T D L T L E D Y G R Y K C 6 135 G R Y K C E V I EG L E D D T 6 136 R Y K C E V I E G L E D D T V 6 137 Y K C E V I E G LE D D T V V 6 143 E G L E D D T V V V A L D L Q 6 144 G L E D D T V V VA L D L Q G 6 150 V V V A L D L Q G V V F P Y F 6 154 L D L Q G V V F PY F P R L G 6 155 D L Q G V V F P Y F P R L G R 6 162 P Y F P R L G R YN L N F H E 6 165 P R L G R Y N L N F H E A Q Q 6 173 N F H E A Q Q A CL D Q D A V 6 174 F H E A Q Q A C L D Q D A V I 6 175 H E A Q Q A C L DQ D A V I A 6 178 Q Q A C L D Q D A V I A S F D 6 180 A C L D Q D A V IA S F D Q L 6 181 C L D Q D A V I A S F D Q L Y 6 190 S F D Q L Y D A WR G G L D W 6 197 A W R G G L D W C N A G W L S 6 198 W R G G L D W C NA G W L S D 6 200 G G L D W C N A G W L S D G S 6 205 C N A G W L S D GS V Q Y P I 6 210 L S D G S V Q Y P I T K P R E 6 213 G S V Q Y P I T KP R E P C G 6 219 I T K P R E P C G G Q N T V P 6 220 T K P R E P C G GQ N T V P G 6 222 P R E P C G G Q N T V P G V R 6 223 R E P C G G Q N TV P G V R N 6 224 E P C G G Q N T V P G V R N Y 6 228 G Q N T V P G V RN Y G F W D 6 236 R N Y G F W D K D K S R Y D V 6 246 S R Y D V F C F TS N F N G R 6 251 F C F T S N F N G R F Y Y L I 6 252 C F T S N F N G RF Y Y L I H 6 253 F T S N F N G R F Y Y L I H P 6 255 S N F N G R F Y YL I H P T K 6 257 F N G R F Y Y L I H P T K L T 6 265 I H P T K L T Y DE A V Q A C 6 266 H P T K L T Y D E A V Q A C L 6 268 T K L T Y D E A VQ A C L N D 6 272 Y D E A V Q A C L N D G A Q I 6 275 A V Q A C L N D GA Q I A K V 6 284 A Q I A K V G Q I F A A W K I 6 292 I F A A W K I L GY D R C D A 6 300 G Y D R C D A G W L A D G S V 6 302 D R C D A G W L AD G S V R Y 6 304 C D A G W L A D G S V R Y P I 6 319 S R P R R R C S PT E A A V R 6 321 P R R R C S P T E A A V R F V 6 323 R R C S P T E A AV R F V G F 6 326 S P T E A A V R F V G F P D K 6 328 T E A A V R F V GF P D K K H 6 330 A A V R F V G F P D K K H K L 6 336 G F P D K K H K LY G V Y C F 6 338 P D K K H K L Y G V Y C F R A 6 97 S M G Y H K K T Y GG Y Q G R 5 105 Y G G Y Q G R V F L K G G S D 5 237 N Y G F W D K D K SR Y D V F 5 56 N V T L P C K F Y R D P T A F 3 22 Y T L D H D R A I H IQ A E N 1 70 F G S G I H K I R I K W T K L 1 72 S G I H K I R I K W T KL T S 1 77 I R I K W T K L T S D Y L K E 1 96 V S M G Y H K K T Y G G YQ G 1 130 T L E D Y G R Y K C E V I E G 1 163 Y F P R L G R Y N L N F HE A 1 215 V Q Y P I T K P R E P C G G Q 1 263 Y L I H P T K L T Y D E AV Q 1 314 V R Y P I S R P R R R C S P T 1 316 Y P I S R P R R R C S P TE A 1 317 P I S R P R R R C S P T E A A 1 318 I S R P R R R C S P T E AA V 1 42 V E A E Q A K V F S H R G G N −5 59 L P C K F Y R D P T A F G SG −5 84 L T S D Y L K E V D V F V S M −5 132 E D Y G R Y K C E V I E G LE −5 193 Q L Y D A W R G G L D W C N A −5 217 Y P I T K P R E P C G G QN T −5 230 N T V P G V R N Y G F W D K D −5 241 W D K D K S R Y D V F CF T S −5 282 D G A Q I A K V G Q I F A A W −5 291 Q I F A A W K I L G YD R C D −5 297 K I L G Y D R C D A G W L A D −5 309 L A D G S V R Y P IS R P R R −5 327 P T E A A V R F V G F P D K K −5 335 V G F P D K K H KL Y G V Y C −5 337 F P D K K H K L Y G V Y C F R −5 151P3D4 v.2: HLAPeptide Scoring Results DRB1*0401 15 - mers SYFPEITHI 111 K L K Y L A FL H K R M N T N 28 281 P A A W L P L R T P W T R P S 28 40 P T K V T G II T Q G A K D F 26 54 F G H V Q F V G S Y K L A Y S 26 51 A K D F G H VQ F V G S Y K L 22 60 V G S Y K L A Y S N D G E H W 22 64 K L A Y S N DG E H W T V Y Q 22 74 W T V Y Q D E K Q R K D K V L 22 158 S E A Y K K VC L S G A P H E 22 233 G F I F K T I A P L A A T R A 22 288 R T P W T RP S S C P T S S S 22 357 N N S W Y V E N G R P A D L A 22 372 G S G Y CG A L W K A I E S L 22 377 G A L W K A I E S L E E G L G 22 14 L H I V VE S I R D H S G Q K 20 26 G Q K M K Q D K K V D L L V P 20 32 D K K V DL L V P T K V T G I 20 73 H W T V Y Q D E K Q R K D K V 20 93 A V V V SC E G I N I S G S F 20 109 R N K L K Y L A F L H K R M N 20 112 L K Y LA F L H K R M N T N P 20 163 K V C L S G A P H E V G W K Y 20 200 K Q LM R L Q K Q A E K N M K 20 229 P R G L G F I F K T I A P L A 20 236 F KT I A P L A A T R A T R I 20 284 W L P L R T P W T R P S S C P 20 313 RN P L P N P R H S P S G G G 20 326 G G G L K K P A R H C Q G Q K 20 7 KT F P L R A L H I V V E S I 18 17 V V E S I R D H S G Q K M K Q 18 33 KK V D L L V P T K V T G I I 18 41 T K V T G I I T Q G A K D F G 18 70 DG E H W T V Y Q D E K Q R K 18 83 R K D K V L L G R K A V V V S 18 101 IN I S G S F C R N K L K Y L 18 134 Q V P S R I F W R Q E K A D G 18 173V G W K Y Q A V T A T L E E K 18 180 V T A T L E E K R K E K A E I 18187 K R K E K A E I H Y R K N K Q 18 196 Y R K N K Q L M R L Q K Q A E18 204 R L Q K Q A E K N M K K K I D 18 237 K T I A P L A A T R A T R IG 18 258 P R A G S S A H R P P A L S A 18 263 S A H R P P A L S A R A PV P 18 272 A R A P V P A A S P A A W L P 18 71 G E H W T V Y Q D E K Q RK D 16 104 S G S F C R N K L K Y L A F L 16 128 R R P Y H F Q V P S R IF W R 16 130 P Y H F Q V P S R I F W R Q E 16 138 R I F W R Q E K A D GG S C C 16 172 E V G W K Y Q A V T A T L E E 16 174 G W K Y Q A V T A TL E E K R 16 193 E I H Y R K N K Q L M R L Q K 16 217 I D K Y T E S P GG G S P R G 16 301 S S T Y D S L S P Y G P R N P 16 358 N S W Y V E N GR P A D L A G 16 36 D L L V P T K V T G I I T Q G 15 170 P H E V G W K YQ A V T A T L 15 191 K A E I H Y R K N K Q L M R L 15 8 T F P L R A L HI V V E S I R 14 11 L R A L H I V V E S I R D H S 14 13 A L H I V V E SI R D H S G Q 14 15 H I V V E S I R D H S G Q K M 14 18 V E S I R D H SG Q K M K Q D 14 35 V D L L V P T K V T G I I T Q 14 57 V Q F V G S Y KL A Y S N D G 14 84 K D K V L L G R K A V V V S C 14 91 R K A V V V S CE G I N I S G 14 92 K A V V V S C E G I N I S G S 14 98 C E G I N I S GS F C R N K L 14 100 G I N I S G S F C R N K L K Y 14 119 H K R M N T NP S R R P Y H F 14 199 N K Q L M R L Q K Q A E K N M 14 202 L M R L Q KQ A E K N M K K K 14 232 L G F I F K T I A P L A A T R 14 239 I A P L AA T R A T R I G H P 14 273 R A P V P A A S P A A W L P L 14 341 H N V LA R G K P Q R K P K S 14 359 S W Y V E N G R P A D L A G S 14 367 P A DL A G S G Y C G A L W K 14 376 C G A L W K A I E S L E E G L 14 380 W KA I E S L E E G L G G K Q 14 383 I E S L E E G L G G K Q K D K 14 3 E HT T K T F P L R A L H I V 12 5 T T K T F P L R A L H I V V E 12 10 P L RA L H I V V E S I R D H 12 12 R A L H I V V E S I R D H S G 12 19 E S IR D H S G Q K M K Q D K 12 23 D H S G Q K M K Q D K K V D L 12 30 K Q DK K V D L L V P T K V T 12 31 Q D K K V D L L V P T K V T G 12 37 L L VP T K V T G I I T Q G A 12 47 I T Q G A K D F G H V Q F V G 12 48 T Q GA K D F G H V Q F V G S 12 53 D F G H V Q F V G S Y K L A Y 12 65 L A YS N D G E H W T V Y Q D 12 67 Y S N D G E H W T V Y Q D E K 12 81 K Q RK D K V L L G R K A V V 12 82 Q R K D K V L L G R K A V V V 12 89 L G RK A V V V S C E G I N I 12 90 G R K A V V V S C E G I N I S 12 95 V V SC E G I N I S G S F C R 12 102 N I S G S F C R N K L K Y L A 12 113 K YL A F L H K R M N T N P S 12 116 A F L H K R M N T N P S R R P 12 124 TN P S R R P Y H F Q V P S R 12 126 P S R R P Y H F Q V P S R I F 12 129R P Y H F Q V P S R I F W R Q 12 135 V P S R I F W R Q E K A D G G 12146 A D G G S C C P Q G H A S E A 12 151 C C P Q G H A S E A Y K K V C12 153 P Q G H A S E A Y K K V C L S 12 167 S G A P H E V G W K Y Q A VT 12 176 K Y Q A V T A T L E E K R K E 12 178 Q A V T A T L E E K R K EK A 12 188 R K E K A E I H Y R K N K Q L 12 189 K E K A E I H Y R K N KQ L M 12 203 M R L Q K Q A E K N M K K K I 12 212 N M K K K I D K Y T ES P G G 12 226 G G S P R G L G F I F K T I A 12 228 S P R G L G F I F KT I A P L 12 230 R G L G F I F K T I A P L A A 12 234 F I F K T I A P LA A T R A T 12 238 T I A P L A A T R A T R I G H 12 241 P L A A T R A TR I G H P G G 12 244 A T R A T R I G H P G G R T P 12 249 R I G H P G GR T P R A G S S 12 251 G H P G G R T P R A G S S A H 12 254 G G R T P RA G S S A H R P P 12 265 H R P P A L S A R A P V P A A 12 268 P A L S AR A P V P A A S P A 12 276 V P A A S P A A W L P L R T P 12 285 L P L RT P W T R P S S C P T 12 291 W T R P S S C P T S S S T Y D 12 292 T R PS S C P T S S S T Y D S 12 295 S S C P T S S S T Y D S L S P 12 305 D SL S P Y G P R N P L P N P 12 310 Y G P R N P L P N P R H S P S 12 327 GG L K K P A R H C Q G Q K H 12 329 L K K P A R H C Q G Q K H N V 12 331K P A R H C Q G Q K H N V L A 12 333 A R H C Q G Q K H N V L A R G 12337 Q G Q K H N V L A R G K P Q R 12 338 G Q K H N V L A R G K P Q R K12 339 Q K H N V L A R G K P Q R K P 12 343 V L A R G K P Q R K P K S EN 12 347 G K P Q R K P K S E N N S W Y 12 350 Q R K P K S E N N S W Y VE N 12 351 R K P K S E N N S W Y V E N G 12 356 E N N S W Y V E N G R PA D L 12 362 V E N G R P A D L A G S G Y C 12 365 G R P A D L A G S G YC G A L 12 382 A I E S L E E G L G G K Q K D 12 384 K S L E E G L G G KQ K D K E 12 386 L E E G L G G K Q K D K E R K 12 390 L G G K Q K D K ER K A E N G 12 392 G K Q K D K E R K A E N G P H 12 395 K D K E R K A EN G P H L L V 12 396 D K E R K A E N G P H L L V E 12 398 E R K A E N GP H L L V E A E 12 6 T K T F P L R A L H I V V E S 11 114 Y L A F L H KR M N T N P S R 11 231 G L G F I F K T I A P L A A T 11 307 L S P Y G PR N P L P N P R H 11 56 H V Q F V G S Y K L A Y S N D 10 137 S R I F W RQ E K A D G G S C 10 85 D K V L L G R K A V V V S C E 9 86 K V L L G R KA V V V S C E G 9 115 L A F L H K R M N T N P S R R 9 132 H F Q V P S RI F W R Q E K A 9 181 T A T L E E K R K E K A E I H 9 210 E K N M K K KI D K Y T E S P 9 267 P P A L S A R A P V P A A S P 9 34 K V D L L V P TK V T G I I T 8 43 V T G I I T Q G A K D F G H V 8 44 T G I I T Q G A KD F G H V Q 8 62 S Y K L A Y S N D G E H W T V 8 161 Y K K V C L S G A PH E V G W 8 177 Y Q A V T A T L E E K R K E K 8 214 K K K I D K Y T E SP G G G S 8 247 A T R I G H P G G R T P R A G 8 304 Y D S L S P Y G P RN P L P N 8 16 I V V E S I R D H S G Q K M K 7 75 T V Y Q D E K Q R K DK V L L 7 198 K N K Q L M R L Q K Q A E K N 7 334 R H C Q G Q K H N V LA R G K 7 2 L E H T T K T F P L R A L H I 6 4 H T T K T F P L R A L H IV V 6 9 F P L R A L H I V V E S I R D 6 20 S I R D H S G Q K M K Q D K K6 29 M K Q D K K V D L L V P T K V 6 38 L V P T K V T G I I T Q G A K 645 G I I T Q G A K D F G H V Q F 6 49 Q G A K D F G H V Q F V G S Y 6 50G A K D F G H V Q F V G S Y K 6 55 G H V Q F V G S Y K L A Y S N 6 59 FV G S Y K L A Y S N D G E H 6 61 G S Y K L A Y S N D G E H W T 6 66 A YS N D G E H W T V Y Q D E 6 76 V Y Q D E K Q R K D K V L L G 6 79 D E KQ R K D K V L L G R K A 6 87 V L L G R K A V V V S C E G I 6 88 L L G RK A V V V S C E G I N 6 94 V V V S C E G I N I S G S F C 6 96 V S C E GI N I S G S F C R N 6 97 S C E G I N I S G S F C R N K 6 99 E G I N I SG S F C R N K L K 6 106 S F C R N K L K Y L A F L H K 6 110 N K L K Y LA F L H K R M N T 6 117 F L H K R M N T N P S R R P Y 6 120 K R M N T NP S R R P Y H F Q 6 121 R M N T N P S R R P Y H F Q V 6 127 S R R P Y HF Q V P S R I F W 6 133 F Q V P S R I F W R Q E K A D 6 140 F W R Q E KA D G G S C C P Q 6 141 W R Q E K A D G G S C C P Q G 6 142 R Q E K A DG G S C C P Q G H 6 143 Q E K A D G G S C C P Q G H A 6 147 D G G S C CP Q G H A S E A Y 6 148 G G S C C P Q G H A S E A Y K 6 149 G S C C P QG H A S E A Y K K 6 150 S C C P Q G H A S E A Y K K V 6 152 C P Q G H AS E A Y K K V C L 6 154 Q G H A S E A Y K K V C L S G 6 155 G H A S E AY K K V C L S G A 6 159 E A Y K K V C L S G A P H E V 6 160 A Y K K V CL S G A P H E V G 6 162 K K V C L S G A P H E V G W K 6 165 C L S G A PH E V G W K Y Q A 6 166 L S G A P H E V G W K Y Q A V 6 168 G A P H E VG W K Y Q A V T A 6 169 A P H E V G W K Y Q A V T A T 6 171 H E V G W KY Q A V T A T L E 6 175 W K Y Q A V T A T L E E K R K 6 179 A V T A T LE E K R K E K A E 6 184 L E E K R K E K A E I H Y R K 6 186 E K R K E KA E I H Y R K N K 6 190 E K A E I H Y R K N K Q L M R 6 195 H Y R K N KQ L M R L Q K Q A 6 197 R K N K Q L M R L Q K Q A E K 6 206 Q K Q A E KN M K K K I D K Y 6 211 K N M K K K I D K Y T E S P G 6 215 K K I D K YT E S P G G G S P 6 216 K I D K Y T E S P G G G S P R 6 220 Y T E S P GG G S P R G L G F 6 221 T E S P G G G S P R G L G F I 6 222 E S P G G GS P R G L G F I F 6 227 G S P R G L G F I F K T I A P 6 246 R A T R I GH P G G R T P R A 6 248 T R I G H P G G R T P R A G S 6 252 H P G G R TP R A G S S A H R 6 255 G R T P R A G S S A H R P P A 6 257 T P R A G SS A H R P P A L S 6 259 R A G S S A H R P P A L S A R 6 261 G S S A H RP P A L S A R A P 6 264 A H R P P A L S A R A P V P A 6 266 R P P A L SA R A P V P A A S 6 269 A L S A R A P V P A A S P A A 6 270 L S A R A PV P A A S P A A W 6 271 S A R A P V P A A S P A A W L 6 274 A P V P A AS P A A W L P L R 6 277 P A A S P A A W L P L R T P W 6 278 A A S P A AW L P L R T P W T 6 279 A S P A A W L P L R T P W T R 6 280 S P A A W LP L R T P W T R P 6 289 T P W T R P S S C P T S S S T 6 290 P W T R P SS C P T S S S T Y 6 293 R P S S C P T S S S T Y D S L 6 294 P S S C P TS S S T Y D S L S 6 296 S C P T S S S T Y D S L S P Y 6 297 C P T S S ST Y D S L S P Y G 6 298 P T S S S T Y D S L S P Y G P 6 299 T S S S T YD S L S P Y G P R 6 300 S S S T Y D S L S P Y G P R N 6 303 T Y D S L SP Y G P R N P L P 6 306 S L S P Y G P R N P L P N P R 6 311 G P R N P LP N P R H S P S G 6 312 P R N P L P N P R H S P S G G 6 316 L P N P R HS P S G G G G L K 6 318 N P R H S P S G G G G L K K P 6 319 P R H S P SG G G G L K K P A 6 320 R H S P S G G G G L K K P A R 6 322 S P S G G GG L K K P A R H C 6 323 P S G G G G L K K P A R H C Q 6 332 P A R H C QG Q K H N V L A R 6 344 L A R G K P Q R K P K S E N N 6 349 P Q R K P KS E N N S W Y V E 6 353 P K S E N N S W Y V E N G R P 6 363 E N G R P AD L A G S G Y C G 6 364 N G R P A D L A G S G Y C G A 6 368 A D L A G SG Y C G A L W K A 6 370 L A G S G Y C G A L W K A I E 6 371 A G S G Y CG A L W K A I E S 6 373 S G Y C G A L W K A I E S L E 6 374 G Y C G A LW K A I E S L E E 6 378 A L W K A I E S L E E G L G G 6 379 L W K A I ES L E E G L G G K 6 381 K A I E S L E E G L G G K Q K 6 397 K E R K A EN G P H L L V E A 6 400 K A E N G P H L L V E A E Q A 6 136 P S R I F WR Q E K A D G G S 3 282 A A W L P L R T P W T R P S S 3 340 K H N V L AR G K P Q R K P K 3 387 E E G L G G K Q K D K E R K A 3 22 R D H S G Q KM K Q D K K V D 1 24 H S G Q K M K Q D K K V D L L 1 27 Q K M K Q D K KV D L L V P T 1 28 K M K Q D K K V D L L V P T K 1 46 I I T Q G A K D FG H V Q F V 1 58 Q F V G S Y K L A Y S N D G E 1 77 Y Q D E K Q R K D KV L L G R 1 78 Q D E K Q R K D K V L L G R K 1 105 G S F C R N K L K Y LA F L H 1 107 F C R N K L K Y L A F L H K R 1 123 N T N P S R R P Y H FQ V P S 1 139 I F W R Q E K A D G G S C C P 1 156 H A S E A Y K K V C LS G A P 1 183 T L E E K R K E K A E I H Y R 1 192 A E I H Y R K N K Q LM R L Q 1 194 I H Y R K N K Q L M R L Q K Q 1 201 Q L M R L Q K Q A E KN M K K 1 205 L Q K Q A E K N M K K K I D K 1 208 Q A E K N M K K K I DK Y T E 1 213 M K K K I D K Y T E S P G G G 1 224 P G G G S P R G L G FI F K T 1 240 A P L A A T R A T R I G H P G 1 253 P G G R T P R A G S SA H R P 1 260 A G S S A H R P P A L S A R A 1 287 L R T P W T R P S S CP T S S 1 314 N P L P N P R H S P S G G G G 1 328 G L K K P A R H C Q GQ K H N 1 342 N V L A R G K P Q R K P K S E 1 346 R G K P Q R K P K S EN N S W 1 348 K P Q R K P K S E N N S W Y V 1 360 W Y V E N G R P A D LA G S G 1 375 Y C G A L W K A I E S L E E G 1 389 G L G G K Q K D K E RK A E N 1 391 G G K Q K D K E R K A E N G P 1 1 M L E H T T K T F P L RA L H −5 80 E K Q R K D K V L L G R K A V −5 103 I S G S F C R N K L K YL A F −5 122 M N T N P S R R P Y H F Q V P −5 157 A S E A Y K K V C L SG A P H −5 182 A T L E E K R K E K A E I H Y −5 185 E E K R K E K A E IH Y R K N −5 209 A E K N M K K K I D K Y T E S −5 243 A A T R A T R I GH P G G R T −5 250 I G H P G G R T P R A G S S A −5 324 S G G G G L K KP A R H C Q G −5 325 G G G G L K K P A R H C Q G Q −5 345 A R G K P Q RK P K S E N N S −5 393 K Q K D K E R K A E N G P H L −5 394 Q K D K E RK A E N G P H L L −5

[0851] TABLE LI SEQ. ID Pos 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 score NO.151P3D4 v.1: HLA Peptide Scoring Results DRB1*1101 15-mers SYFPEITHI 235V R N Y G F W D K D K S R Y D 25 161 F P Y F P R L G R Y N L N F H 24258 N G R F Y Y L I H P T K L T Y 24 18 L S D N Y T L D H D R A I H I 22289 V G Q I F A A W K I L G Y D R 22 315 R Y P I S R P R R R C S P T E21 95 F V S M G Y H K K T Y G G Y Q 20 237 N Y G F W D K D K S R Y D V F20 295 A W K I L G Y D R C D A G W L 20 67 P T A F G S G I H K I R I K W19 86 S D Y L K E V D V F V S M G Y 19 105 Y G G Y Q G R V F L K G G S D19 334 F V G F P D K K H K L Y G V Y 19 4 L L L L V L I S I C W A D H L18 78 R I K W T K L T S D Y L K E V 18 158 G V V F P Y F P R L G R Y N L18 167 L G R Y N L N F H E A Q Q A C 18 283 G A Q I A K V G Q I F A A WK 18 293 F A A W K I L G Y D R C D A G 18 92 V D V F V S M G Y H K K T YG 17 214 S V Q Y P I T K P R E P C G G 17 259 G R F Y Y L I H P T K L TY D 17 325 C S P T E A A V R F V G F P D 17 44 A E Q A K V F S H R G G NV T 16 54 G G N V T L P C K F Y R D P T 16 60 P C K F Y R D P T A F G SG I 16 61 C K F Y R D P T A F G S G I H 16 68 T A F G S G I H K I R I KW T 16 188 I A S F D Q L Y D A W R G G L 16 213 G S V Q Y P I T K P R EP C G 16 228 G Q N T V P G V R N Y G F W D 16 248 Y D V F C F T S N F NG R F Y 16 312 G S V R Y P I S R P R R R C S 16 93 D V F V S M G Y H K KT Y G G 15 107 G Y Q G R V F L K G G S D S D 15 128 D L T L E D Y G R YK C E V I 15 157 Q G V V F P Y F P R L G R Y N 15 1 M K S L L L L V L IS I C W A 14 9 L I S I C W A D H L S D N Y T 14 23 T L D H D R A I H I QA E N G 14 40 L L V E A E Q A K V F S H R G 14 43 E A E Q A K V F S H RG G N V 14 75 H K I R I K W T K L T S D Y L 14 123 S L V I T D L T L E DY G R Y 14 153 A L D L Q G V V F P Y F P R L 14 191 F D Q L Y D A W R GG L D W C 14 216 Q Y P I T K P R E P C G G Q N 14 250 V F C F T S N F NG R F Y Y L 14 261 F Y Y L I H P T K L T Y D E A 14 264 L I H P T K L TY D E A V Q A 14 267 P T K L T Y D E A V Q A C L N 14 280 L N D G A Q IA K V G Q I F A 14 316 Y P I S R P R R R C S P T E A 14 332 V R F V G FP D K K H K L Y G 14 335 V G F P D K K H K L Y G V Y C 14 2 K S L L L LV L I S I C W A D 13 3 S L L L L V L I S I C W A D H 13 19 S D N Y T L DH D R A I H I Q 13 56 N V T L P C K F Y R D P T A F 13 109 Q G R V F L KG G S D S D A S 13 142 I E G L E D D T V V V A L D L 13 147 D D T V V VA L D L Q G V V F 13 154 L D L Q G V V F P Y F P R L G 13 306 A G W L AD G S V R Y P I S R 13 308 W L A D G S V R Y P I S R P R 13 313 S V R YP I S R P R R R C S P 13 6 L L V L I S I C W A D H L S D 12 26 H D R A IH I Q A E N G P H L 12 27 D R A I H I Q A E N G P H L L 12 36 N G P H LL V E A E Q A K V F 12 71 G S G I H K I R I K W T K L T 12 85 T S D Y LK E V D V F V S M G 12 88 Y L K E V D V F V S M G Y H K 12 102 K K T Y GG Y Q G R V F L K G 12 106 G G Y Q G R V F L K G G S D S 12 111 R V F LK G G S D S D A S L V 12 134 Y G R Y K C E V I E G L E D D 12 139 C E VI E G L E D D T V V V A 12 148 D T V V V A L D L Q G V V F P 12 151 V VA L D L Q G V V F P Y F P 12 160 V F P Y F P R L G R Y N L N F 12 166 RL G R Y N L N F H E A Q Q A 12 169 R Y N L N F H E A Q Q A C L D 12 179Q A C L D Q D A V I A S F D Q 12 196 D A W R G G L D W C N A G W L 12207 A G W L S D G S V Q Y P I T K 12 229 Q N T V P G V R N Y G F W D K12 244 D K S R Y D V F C F T S N F N 12 269 K L T Y D E A V Q A C L N DG 12 273 D E A V Q A C L N D G A Q I A 12 286 I A K V G Q I F A A W K IL G 12 296 W K I L G Y D R C D A G W L A 12 305 D A G W L A D G S V R YP I S 12 329 E A A V R F V G F P D K K H K 12 47 A K V F S H R G G N V TL P C 11 131 L E D Y G R Y K C E V I E G L 11 145 L E D D T V V V A L DL Q G V 11 192 D Q L Y D A W R G G L D W C N 11 238 Y G F W D K D K S RY D V F C 11 245 K S R Y D V F C F T S N F N G 11 254 T S N F N G R F YY L I H P T 11 260 R F Y Y L I H P T K L T Y D E 11 314 V R Y P I S R PR R R C S P T 11 331 A V R F V G F P D K K H K L Y 11 11 S I C W A D H LS D N Y T L D 10 97 S M G Y H K K T Y G G Y Q G R 10 110 G R V F L K G GS D S D A S L 10 126 I T D L T L E D Y G R Y K C E 10 171 N L N F H E AQ Q A C L D Q D 10 195 Y D A W R G G L D W C N A G W 10 201 G L D W C NA G W L S D G S V 10 206 N A G W L S D G S V Q Y P I T 10 290 G Q I F AA W K I L G Y D R C 10 298 I L G Y D R C D A G W L A D G 10 307 G W L AD G S V R Y P I S R P 10 333 R F V G F P D K K H K L Y G V 10 20 D N Y TL D H D R A I H I Q A 9 31 H I Q A E N G P H L L V E A E 9 70 F G S G IH K I R I K W T K L 9 82 T K L T S D Y L K E V D V F V 9 89 L K E V D VF V S M G Y H K K 9 144 G L E D D T V V V A L D L Q G 9 35 E N G P H L LV E A E Q A K V 8 45 E Q A K V F S H R G G N V T L 8 57 V T L P C K F YR D P T A F G 8 72 S G I H K I R I K W T K L T S 8 81 W T K L T S D Y LK E V D V F 8 91 E V D V F V S M G Y H K K T Y 8 94 V F V S M G Y H K KT Y G G Y 8 103 K T Y G G Y Q G R V F L K G G 8 118 S D S D A S L V I TD L T L E 8 130 T L E D Y G R Y K C E V I E G 8 146 E D D T V V V A L DL Q G V V 8 156 L Q G V V F P Y F P R L G R Y 8 189 A S F D Q L Y D A WR G G L D 8 215 V Q Y P I T K P R E P C G G Q 8 226 C G G Q N T V P G VR N Y G F 8 239 G F W D K D K S R Y D V F C F 8 252 C F T S N F N G R FY Y L I H 8 310 A D G S V R Y P I S R P R R R 8 8 V L I S I C W A D H LS D N Y 7 37 G P H L L V E A E Q A K V F S 7 38 P H L L V E A E Q A K VF S H 7 39 H L L V E A E Q A K V F S H R 7 46 Q A K V F S H R G G N V TL P 7 49 V F S H R G G N V T L P C K F 7 73 G I H K I R I K W T K L T SD 7 74 I H K I R I K W T K L T S D Y 7 119 D S D A S L V I T D L T L E D7 120 S D A S L V I T D L T L E D Y 7 121 D A S L V I T D L T L E D Y G7 135 G R Y K C E V I E G L E D D T 7 136 R Y K C E V I E G L E D D T V7 149 T V V V A L D L Q G V V F P Y 7 150 V V V A L D L Q G V V F P Y F7 178 Q Q A C L D Q D A V I A S F D 7 182 L D Q D A V I A S F D Q L Y D7 184 Q D A V I A S F D Q L Y D A W 7 190 S F D Q L Y D A W R G G L D W7 200 G G L D W C N A G W L S D G S 7 209 W L S D G S V Q Y P I T K P R7 211 S D G S V Q Y P I T K P R E P 7 222 P R E P C G G Q N T V P G V R7 247 R Y D V F C F T S N F N G R F 7 270 L T Y D E A V Q A C L N D G A7 276 V Q A C L N D G A Q I A K V G 7 279 C L N D G A Q I A K V G Q I F7 284 A Q I A K V G Q I F A A W K I 7 299 L G Y D R C D A G W L A D G S7 311 D G S V R Y P I S R P R R R C 7 327 P T E A A V R F V G F P D K K7 5 L L L V L I S I C W A D H L S 6 7 L V L I S I C W A D H L S D N 6 12I C W A D H L S D N Y T L D H 6 15 A D H L S D N Y T L D H D R A 6 21 NY T L D H D R A I H I Q A E 6 24 L D H D R A I H I Q A E N G P 6 29 A IH I Q A E N G P H L L V E 6 33 Q A E N G P H L L V E A E Q A 6 34 A E NG P H L L V E A E Q A K 6 51 S H R G G N V T L P C K F Y R 6 53 R G G NV T L P C K F Y R D P 6 58 T L P C K F Y R D P T A F G S 6 62 K F Y R DP T A F G S G I H K 6 76 K I R I K W T K L T S D Y L K 6 83 K L T S D YL K E V D V F V S 6 90 K E V D V F V S M G Y H K K T 6 96 V S M G Y H KK T Y G G Y Q G 6 99 G Y H K K T Y G G Y Q G R V F 6 108 Y Q G R V F L KG G S D S D A 6 112 V F L K G G S D S D A S L V I 6 122 A S L V I T D LT L E D Y G R 6 124 L V I T D L T L E D Y G R Y K 6 125 V I T D L T L ED Y G R Y K C 6 133 D Y G R Y K C E V I E G L E D 6 138 K C E V I E G LE D D T V V V 6 164 F P R L G R Y N L N F H E A Q 6 175 H E A Q Q A C LD Q D A V I A 6 176 E A Q Q A C L D Q D A V I A S 6 181 C L D Q D A V IA S F D Q L Y 6 185 D A V I A S F D Q L Y D A W R 6 186 A V I A S F D QL Y D A W R G 6 197 A W R G G L D W C N A G W L S 6 199 R G G L D W C NA G W L S D G 6 202 L D W C N A G W L S D G S V Q 6 203 D W C N A G W LS D G S V Q Y 6 204 W C N A G W L S D G S V Q Y P 6 212 D G S V Q Y P IT K P R E P C 6 217 Y P I T K P R E P C G G Q N T 6 223 R E P C G G Q NT V P G V R N 6 232 V P G V R N Y G F W D K D K S 6 256 N F N G R F Y YL I H P T K L 6 262 Y Y L I H P T K L T Y D E A V 6 272 Y D E A V Q A CL N D G A Q I 6 274 E A V Q A C L N D G A Q I A K 6 277 Q A C L N D G AQ I A K V G Q 6 292 I F A A W K I L G Y D R C D A 6 301 Y D R C D A G WL A D G S V R 6 302 D R C D A G W L A D G S V R Y 6 303 R C D A G W L AD G S V R Y P 6 319 S R P R R R C S P T E A A V R 6 320 R P R R R C S PT E A A V R F 6 326 S P T E A A V R F V G F P D K 6 338 P D K K H K L YG V Y C F R A 6 227 G G Q N T V P G V R N Y G F W 4 64 Y R D P T A F G SG I H K I R 3 87 D Y L K E V D V F V S M G Y H 3 225 P C G G Q N T V P GV R N Y G 3 282 D G A Q I A K V G Q I F A A W 3 324 R C S P T E A A V RF V G F P 3 330 A A V R F V G F P D K K H K L 3 42 V E A E Q A K V F S HR G G N 2 50 F S H R G G N V T L P C K F Y 2 52 H R G G N V T L P C K FY R D 2 55 G N V T L P C K F Y R D P T A 2 66 D P T A F G S G I H K I RI K 2 69 A F G S G I H K I R I K W T K 2 100 Y H K K T Y G G Y Q G R V FL 2 101 H K K T Y G G Y Q G R V F L K 2 143 E G L E D D T V V V A L D LQ 2 152 V A L D L Q G V V F P Y F P R 2 159 V V F P Y F P R L G R Y N LN 2 180 A C L D Q D A V I A S F D Q L 2 208 G W L S D G S V Q Y P I T KP 2 243 K D K S R Y D V F C F T S N F 2 323 R R C S P T E A A V R F V GF 2 328 T E A A V R F V G F P D K K H 2 340 K K H K L Y G V Y C F R A YN 2 14 W A D H L S D N Y T L D H D R 1 22 Y T L D H D R A I H I Q A E N1 30 I H I Q A E N G P H L L V E A 1 32 I Q A E N G P H L L V E A E Q 159 L P C K F Y R D P T A F G S G 1 79 I K W T K L T S D Y L K E V D 1 80K W T K L T S D Y L K E V D V 1 84 L T S D Y L K E V D V F V S M 1 104 TY G G Y Q G R V F L K G G S 1 114 L K G G S D S D A S L V I T D 1 115 KG G S D S D A S L V I T D L 1 116 G G S D S D A S L V I T D L T 1 127 TD L T L E D Y G R Y K C E V 1 132 E D Y G R Y K C E V I E G L E 1 140 EV I E G L E D D T V V V A L 1 141 V I E G L E D D T V V V A L D 1 155 DL Q G V V F P Y F P R L G R 1 162 P Y F P R L G R Y N L N F H E 1 170 YN L N F H E A Q Q A C L D Q 1 172 L N F H E A Q Q A C L D Q D A 1 177 AQ Q A C L D Q D A V I A S F 1 187 V I A S F D Q L Y D A W R G G 1 205 CN A G W L S D G S V Q Y P I 1 210 L S D G S V Q Y P I T K P R E 1 230 NT V P G V R N Y G F W D K D 1 233 P G V R N Y G F W D K D K S R 1 236 RN Y G F W D K D K S R Y D V 1 240 F W D K D K S R Y D V F C F T 1 249 DV F C F T S N F N G R F Y Y 1 251 F C F T S N F N G R F Y Y L I 1 253 FT S N F N G R F Y Y L I H P 1 255 S N F N G R F Y Y L I H P T K 1 257 FN G R F Y Y L I H P T K L T 1 266 H P T K L T Y D E A V Q A C L 1 271 TY D E A V Q A C L N D G A Q 1 278 A C L N D G A Q I A K V G Q I 1 287 AK V G Q I F A A W K I L G Y 1 288 K V G Q I F A A W K I L G Y D 1 294 AA W K I L G Y D R C D A G W 1 304 C D A G W L A D G S V R Y P I 1 309 LA D G S V R Y P I S R P R R 1 322 R R R C S P T E A A V R F V G 1 337 FP D K K H K L Y G V Y C F R 1 151P3D4 v.2: HLA Peptide Scoring ResultsDRB1*1101 15-mers SYFPEITHI 229 P R G L G F I F K T I A P L A 27 137 S RI F W R Q E K A D G G S C 24 44 T G I I T Q G A K D F G H V Q 22 51 A KD F G H V Q F V G S Y K L 22 158 S E A Y K K V C L S G A P H E 22 233 GF I F K T I A P L A A T R A 22 244 A T R A T R I G H P G G R T P 22 301S S T Y D S L S P Y G P R N P 22 338 G Q K H N V L A R G K P Q R K 22 34K V D L L V P T K V T G I I T 21 112 L K Y L A F L H K R M N T N P 21163 K V C L S G A P H E V G W K Y 21 181 T A T L E E K R K E K A E I H21 14 L H I V V E S I R D H S G Q K 20 40 P T K V T G I I T Q G A K D F20 111 K L K Y L A F L H K R M N T N 20 199 N K Q L M R L Q K Q A E K NM 20 236 F K T I A P L A A T R A T R I 20 313 R N P L P N P R H S P S GG G 20 130 P Y H F Q V P S R I F W R Q E 19 380 W K A I E S L E E G L GG K Q 19 15 H I V V E S I R D H S G Q K M 18 56 H V Q F V G S Y K L A YS N D 18 217 I D K Y T E S P G G G S P R G 18 357 N N S W Y V E N G R PA D L A 18 358 N S W Y V E N G R P A D L A G 18 174 G W K Y Q A V T A TL E E K R 17 60 V G S Y K L A Y S N D G E H W 16 73 H W T V Y Q D E K QR K D K V 16 138 R I F W R Q E K A D G G S C C 16 281 P A A W L P L R TP W T R P S 16 285 L P L R T P W T R P S S C P T 16 377 G A L W K A I ES L E E G L G 16 11 L R A L H I V V E S I R D H S 15 32 D K K V D L L VP T K V T G I 15 82 Q R K D K V L L G R K A V V V 15 84 K D K V L L G RK A V V V S C 15 89 L G R K A V V V S C E G I N I 15 105 G S F C R N K LK Y L A F L H 15 119 H K R M N T N P S R R P Y H F 15 168 G A P H E V GW K Y Q A V T A 15 207 K Q A E K N M K K K I D K Y T 15 222 E S P G G GS P R G L G F I F 15 257 T P R A G S S A H R P P A L S 15 344 L A R G KP Q R K P K S E N N 15 373 S G Y C G A L W K A I E S L E 15 387 E E G LG G K Q K D K E R K A 15 26 G Q K M K Q D K K V D L L V P 14 71 G E H WT V Y Q D E K Q R K D 14 83 R K D K V L L G R K A V V V S 14 128 R R P YH F Q V P S R I F W R 14 196 Y R K N K Q L M R L Q K Q A E 14 211 K N MK K K I D K Y T E S P G 14 232 L G F I F K T I A P L A A T R 14 251 G HP G G R T P R A G S S A H 14 258 P R A G S S A H R P P A L S A 14 312 PR N P L P N P R H S P S G G 14 322 S P S G G G G L K K P A R H C 14 323P S G G G G L K K P A R H C Q 14 326 G G G L K K P A R H C Q G Q K 14327 G G L K K P A R H C Q G Q K H 14 340 K H N V L A R G K P Q R K P K14 356 E N N S W Y V E N G R P A D L 14 8 T F P L R A L H I V V E S I R13 29 M K Q D K K V D L L V P T K V 13 54 F G H V Q F V G S Y K L A Y S13 86 K V L L G R K A V V V S C E G 13 93 A V V V S C E G I N I S G S F13 247 A T R I G H P G G R T P R A G 13 264 A H R P P A L S A R A P V PA 13 279 A S P A A W L P L R T P W T R 13 284 W L P L R T P W T R P S SC P 13 304 Y D S L S P Y G P R N P L P N 13 57 V Q F V G S Y K L A Y S ND G 12 74 W T V Y Q D E K Q R K D K V L 12 95 V V S C E G I N I S G S FC R 12 109 R N K L K Y L A F L H K R M N 12 115 L A F L H K R M N T N PS R R 12 116 A F L H K R M N T N P S R R P 12 179 A V T A T L E E K R KE K A E 12 214 K K K I D K Y T E S P G G G S 12 267 P P A L S A R A P VP A A S P 12 270 L S A R A P V P A A S P A A W 12 288 R T P W T R P S SC P T S S S 12 367 P A D L A G S G Y C G A L W K 12 4 H T T K T F P L RA L H I V V 11 6 T K T F P L R A L H I V V E S 11 120 K R M N T N P S RR P Y H F Q 11 2 L E H T T K T F P L R A L H I 10 50 G A K D F G H V Q FV G S Y K 10 64 K L A Y S N D G E H W T V Y Q 10 103 I S G S F C R N K LK Y L A F 10 104 S G S F C R N K L K Y L A F L 10 114 Y L A F L H K R MN T N P S R 10 172 E V G W K Y Q A V T A T L E E 10 187 K R K E K A E IH Y R K N K Q 10 193 E I H Y R K N K Q L M R L Q K 10 231 G L G F I F KT I A P L A A T 10 241 P L A A T R A T R I G H P G G 10 307 L S P Y G PR N P L P N P R H 10 336 C Q G Q K H N V L A R G K P Q 10 372 G S G Y CG A L W K A I E S L 10 389 G L G G K Q K D K E R K A E N 10 7 K T F P LR A L H I V V E S I 9 12 R A L H I V V E S I R D H S G 9 20 S I R D H SG Q K M K Q D K K 9 25 S G Q K M K Q D K K V D L L V 9 36 D L L V P T KV T G I I T Q G 9 37 L L V P T K V T G I I T Q G A 9 55 G H V Q F V G SY K L A Y S N 9 76 V Y Q D E K Q R K D K V L L G 9 78 Q D E K Q R K D KV L L G R K 9 101 I N I S G S F C R N K L K Y L 9 113 K Y L A F L H K RM N T N P S 9 129 R P Y H F Q V P S R I F W R Q 9 154 Q G H A S E A Y KK V C L S G 9 177 Y Q A V T A T L E E K R K E K 9 190 E K A E I H Y R KN K Q L M R 9 192 A E I H Y R K N K Q L M R L Q 9 206 Q K Q A E K N M KK K I D K Y 9 333 A R H C Q G Q K H N V L A R G 9 385 S L E E G L G G KQ K D K E R 9 398 E R K A E N G P H L L V E A E 9 10 P L R A L H I V V ES I R D H 8 13 A L H I V V E S I R D H S G Q 8 16 I V V E S I R D H S GQ K M K 8 22 R D H S G Q K M K Q D K K V D 8 48 T Q G A K D F G H V Q FV G S 8 65 L A Y S N D G E H W T V Y Q D 8 75 T V Y Q D E K Q R K D K VL L 8 81 K Q R K D K V L L G R K A V V 8 88 L L G R K A V V V S C E G IN 8 91 R K A V V V S C E G I N I S G 8 121 R M N T N P S R R P Y H F Q V8 124 T N P S R R P Y H F Q V P S R 8 132 H F Q V P S R I F W R Q E K A8 134 Q V P S R I F W R Q E K A D G 8 148 G G S C C P Q G H A S E A Y K8 155 G H A S E A Y K K V C L S G A 8 157 A S E A Y K K V C L S G A P H8 178 Q A V T A T L E E K R K E K A 8 180 V T A T L E E K R K E K A E I8 183 T L E E K R K E K A E I H Y R 8 188 R K E K A E I H Y R K N K Q L8 189 K E K A E I H Y R K N K Q L M 8 203 M R L Q K Q A E K N M K K K I8 208 Q A E K N M K K K I D K Y T E 8 220 Y T E S P G G G S P R G L G F8 238 T I A P L A A T R A T R I G H 8 239 I A P L A A T R A T R I G H P8 240 A P L A A T R A T R I G H P G 8 248 T R I G H P G G R T P R A G S8 249 R I G H P G G R T P R A G S S 8 253 P G G R T P R A G S S A H R P8 256 R T P R A G S S A H R P P A L 8 263 S A H R P P A L S A R A P V P8 265 H R P P A L S A R A P V P A A 8 269 A L S A R A P V P A A S P A A8 280 S P A A W L P L R T P W T R P 8 283 A W L P L R T P W T R P S S C8 295 S S C P T S S S T Y D S L S P 8 305 D S L S P Y G P R N P L P N P8 310 Y G P R N P L P N P R H S P S 8 332 P A R H C Q G Q K H N V L A R8 341 H N V L A R G K P Q R K P K S 8 342 N V L A R G K P Q R K P K S E8 343 V L A R G K P Q R K P K S E N 8 346 R G K P Q R K P K S E N N S W8 390 L G G K Q K D K E R K A E N G 8 391 G G K Q K D K E R K A E N G P8 392 G K Q K D K E R K A E N G P H 8 5 T T K T F P L R A L H I V V E 718 V E S I R D H S G Q K M K Q D 7 23 D H S G Q K M K Q D K K V D L 7 33K K V D L L V P T K V T G I I 7 79 D E K Q R K D K V L L G R K A 7 85 DK V L L G R K A V V V S C E 7 90 G R K A V V V S C E G I N I S 7 100 G IN I S G S F C R N K L K Y 7 125 N P S R R P Y H F Q V P S R I 7 133 F QV P S R I F W R Q E K A D 7 135 V P S R I F W R Q E K A D G G 7 136 P SR I F W R Q E K A D G G S 7 156 H A S E A Y K K V C L S G A P 7 159 E AY K K V C L S G A P H E V 7 170 P H E V G W K Y Q A V T A T L 7 197 R KN K Q L M R L Q K Q A E K 7 230 R G L G F I F K T I A P L A A 7 250 I GH P G G R T P R A G S S A 7 260 A G S S A H R P P A L S A R A 7 266 R PP A L S A R A P V P A A S 7 271 S A R A P V P A A S P A A W L 7 275 P VP A A S P A A W L P L R T 7 297 C P T S S S T Y D S L S P Y G 7 306 S LS P Y G P R N P L P N P R 7 311 G P R N P L P N P R H S P S G 7 321 H SP S G G G G L K K P A R H 7 334 R H C Q G Q K H N V L A R G K 7 337 Q GQ K H N V L A R G K P Q R 7 360 W Y V E N G R P A D L A G S G 7 371 A GS G Y C G A L W K A I E S 7 376 C G A L W K A I E S L E E G L 7 383 I ES L E E G L G G K Q K D K 7 9 F P L R A L H I V V E S I R D 6 31 Q D K KV D L L V P T K V T G 6 35 V D L L V P T K V T G I I T Q 6 39 V P T K VT G I I T Q G A K D 6 41 T K V T G I I T Q G A K D F G 6 43 V T G I I TQ G A K D F G H V 6 59 F V G S Y K L A Y S N D G E H 6 62 S Y K L A Y SN D G E H W T V 6 70 D G E H W T V Y Q D E K Q R K 6 92 K A V V V S C EG I N I S G S 6 94 V V V S C E G I N I S G S F C 6 97 S C E G I N I S GS F C R N K 6 98 C E G I N I S G S F C R N K L 6 106 S F C R N K L K Y LA F L H K 6 126 P S R R P Y H F Q V P S R I F 6 139 I F W R Q E K A D GG S C C P 6 142 R Q E K A D G G S C C P Q G H 6 144 E K A D G G S C C PQ G H A S 6 146 A D G G S C C P Q G H A S E A 6 147 D G G S C C P Q G HA S E A Y 6 149 G S C C P Q G H A S E A Y K K 6 160 A Y K K V C L S G AP H E V G 6 161 Y K K V C L S G A P H E V G W 6 167 S G A P H E V G W KY Q A V T 6 171 H E V G W K Y Q A V T A T L E 6 191 K A E I H Y R K N KQ L M R L 6 198 K N K Q L M R L Q K Q A E K N 6 200 K Q L M R L Q K Q AE K N M K 6 202 L M R L Q K Q A E K N M K K K 6 210 E K N M K K K I D KY T E S P 6 212 N M K K K I D K Y T E S P G G 6 213 M K K K I D K Y T ES P G G G 6 215 K K I D K Y T E S P G G G S P 6 216 K I D K Y T E S P GG G S P R 6 218 D K Y T E S P G G G S P R G L 6 226 G G S P R G L G F IF K T I A 6 242 L A A T R A T R I G H P G G R 6 243 A A T R A T R I G HP G G R T 6 252 H P G G R T P R A G S S A H R 6 261 G S S A H R P P A LS A R A P 6 268 P A L S A R A P V P A A S P A 6 272 A R A P V P A A S PA A W L P 6 273 R A P V P A A S P A A W L P L 6 282 A A W L P L R T P WT R P S S 6 287 L R T P W T R P S S C P T S S 6 289 T P W T R P S S C PT S S S T 6 290 P W T R P S S C P T S S S T Y 6 291 W T R P S S C P T SS S T Y D 6 298 P T S S S T Y D S L S P Y G P 6 300 S S S T Y D S L S PY G P R N 6 308 S P Y G P R N P L P N P R H S 6 314 N P L P N P R H S PS G G G G 6 315 P L P N P R H S P S G G G G L 6 316 L P N P R H S P S GG G G L K 6 317 P N P R H S P S G G G G L K K 6 348 K P Q R K P K S E NN S W Y V 6 354 K S E N N S W Y V E N G R P A 6 359 S W Y V E N G R P AD L A G S 6 361 Y V E N G R P A D L A G S G Y 6 362 V E N G R P A D L AG S G Y C 6 363 E N G R P A D L A G S G Y C G 6 364 N G R P A D L A G SG Y C G A 6 366 R P A D L A G S G Y C G A L W 6 374 G Y C G A L W K A IE S L E E 6 378 A L W K A I E S L E E G L G G 6 381 K A I E S L E E G LG G K Q K 6 384 E S L E E G L G G K Q K D K E 6 393 K Q K D K E R K A EN G P H L 6 394 Q K D K E R K A E N G P H L L 6 400 K A E N G P H L L VE A E Q A 6 1 M L E H T T K T F P L R A L H 3 28 K M K Q D K K V D L L VP T K 3 166 L S G A P H E V G W K Y Q A V 3 53 D F G H V Q F V G S Y K LA Y 2 69 N D G E H W T V Y Q D E K Q R 2 80 E K Q R K D K V L L G R K AV 2 87 V L L G R K A V V V S C E G I 2 99 E G I N I S G S F C R N K L K2 118 L H K R M N T N P S R R P Y H 2 173 V G W K Y Q A V T A T L E E K2 194 I H Y R K N K Q L M R L Q K Q 2 195 H Y R K N K Q L M R L Q K Q A2 234 F I F K T I A P L A A T R A T 2 246 R A T R I G H P G G R T P R A2 278 A A S P A A W L P L R T P W T 2 299 T S S S T Y D S L S P Y G P R2 303 T Y D S L S P Y G P R N P L P 2 324 S G G G G L K K P A R H C Q G2 355 S E N N S W Y V E N G R P A D 2 3 E H T T K T F P L R A L H I V 124 H S G Q K M K Q D K K V D L L 1 27 Q K M K Q D K K V D L L V P T 1 30K Q D K K V D L L V P T K V T 1 38 L V P T K V T G I I T Q G A K 1 42 KV T G I I T Q G A K D F G H 1 47 I T Q G A K D F G H V Q F V G 1 52 K DF G H V Q F V G S Y K L A 1 66 A Y S N D G E H W T V Y Q D E 1 77 Y Q DE K Q R K D K V L L G R 1 102 N I S G S F C R N K L K Y L A 1 108 C R NK L K Y L A F L H K R M 1 110 N K L K Y L A F L H K R M N T 1 152 C P QG H A S E A Y K K V C L 1 153 P Q G H A S E A Y K K V C L S 1 175 W K YQ A V T A T L E E K R K 1 184 L E E K R K E K A E I H Y R K 1 201 Q L MR L Q K Q A E K N M K K 1 204 R L Q K Q A E K N M K K K I D 1 205 L Q KQ A E K N N K K K I D K 1 209 A E K N M K K K I D K Y T E S 1 221 T E SP G G G S P R G L G F I 1 225 G G G S P R G L G F I F K T I 1 227 G S PR G L G F I F K T I A P 1 237 K T I A P L A A T R A T R I G 1 277 P A AS P A A W L P L R T P W 1 319 P R H S P S G G G G L K K P A 1 320 R H SP S G G G G L K K P A R 1 325 G G G G L K K P A R H C Q G Q 1 330 K K PA R H C Q G Q K H N V L 1 352 K P K S E N N S W Y V E N G R 1 369 D L AG S G Y C G A L W K A I 1 397 K E R K A E N G P H L L V E A 1 399 R K AK N G P H L L V E A E Q 1

[0852] TABLE LII Exon Number Start End (A). Exon compositions of 151P3D4v.1 Exon 1 1 289 Exon 2 290 415 Exon 3 416 787 Exon 4 788 1090 Exon 51091 1957 (B). Exon compositions of 151P3D4 v.2 Exon 1 1 102 Exon 2 103258 Exon 3 259 425 Exon 4 426 667 Exon 5 668 863 Exon 6 864 999 Exon 71000 1201 Exon 8 1202 1573 Exon 9 1574 1876 Exon 10 1877 2166

[0853] TABLE LIII Nucleotide sequence of transcript variant 151P3D4 v.2atgttggagc atactactaa gacattcccc ttaagagcac tgcacatagt tgtggaaagc 60attagggacc acagtggcca aaaaatgaag caggataaga aggtggatct tcttgttcca 120accaaagtga ctggcatcat tacacaagga gctaaagatt ttggtcatgt acagtttgtt 180ggctcctaca aactggctta cagcaatgat ggagaacact ggactgtata ccaggatgaa 240aagcaaagaa aagataaggt actgctgggc cggaaggcgg tggtcgtaag ctgcgaaggc 300atcaacattt ctggcagttt ctgcagaaac aagttgaagt acctggcttt cctccacaag 360cggatgaaca ccaacccttc tcgacgcccc taccacttcc aggtccccag ccgcatcttc 420tggcgacaag aaaaagcaga tggtggttcc tgctgccctc aaggtcatgc gtctgaagcc 480tacaagaaag tttgcctatc tggggcgcct cacgaggttg gctggaagta ccaggcagtg 540acagccaccc tggaggaaaa gaggaaagag aaagccgaga tccactaccg gaagaataaa 600cagctcatga ggctacagaa acaggccgag aagaacatga agaagaaaat tgacaaatac 660acagagagtc caggaggagg cagtccccgt ggcttaggct ttatctttaa gacaatagcg 720ccgctcgccg ccacccgcgc gactcggatc gggcatcccg gcggccgcac cccgcgcgct 780ggctcatctg cacaccggcc acctgcattg tcggccagag cccccgtccc ggcggcttcc 840ccagcagctt ggctgcccct caggacgccc tggacccgcc catcctcctg ccccactagc 900tcatcgactt acgactccct cagtccctac ggcccacgga accctctccc caacccgcgc 960cacagcccga gcggcggcgg cggccttaag aagcccgcaa gacactgtca aggtcaaaag 1020cacaatgtgc tagccagggg gaaaccccag agaaagccaa aatctgaaaa taacagctgg 1080tatgtagaaa acggcagacc tgctgacttg gcaggctcag gatattgtgg tgctctttgg 1140aaggcaatag agtccttgga ggaaggactt ggaggaaaac aaaaggacaa ggaaaggaaa 1200gcagaaaatg gcccccatct acttgtggaa gcagagcaag ccaaggtgtt ttcacacaga 1260ggtggcaatg ttacactgcc atgtaaattt tatcgagacc ctacagcatt tggctcagga 1320atccataaaa tccgaattaa gtggaccaag ctaacttcgg attacctcaa ggaagtggat 1380gtttttgttt ccatgggata ccacaaaaaa acctatggag gctaccaggg tagagtgttt 1440ctgaagggag gcagtgatag tgatgcttct ctggtcatca cagacctcac tctggaagat 1500tatgggagat ataagtgtga ggtgattgaa ggattagaag atgatactgt tgtggtagca 1560ctggacttac aaggtgtggt attcccttac tttccacgac tggggcgcta caatctcaat 1620tttcacgagg cgcagcaggc gtgtctggac caggatgctg tgatcgcctc cttcgaccag 1680ctgtacgacg cctggcgggg cgggctggac tggtgcaatg ccggctggct cagtgatggc 1740tctgtgcaat atcccatcac aaagcccaga gagccctgtg gggggcagaa cacagtgccc 1800ggagtcagga actacggatt ttgggataaa gataaaagca gatatgatgt tttctgtttt 1860acatccaatt tcaatggccg tttttactat ctgatccacc ccaccaaact gacctatgat 1920gaagcggtgc aagcttgtct caatgatggt gctcagattg caaaagtggg ccagatattt 1980gctgcctgga aaattctcgg atatgaccgc tgtgatgcgg gctggttggc ggatggcagc 2040gtccgctacc ccatctctag gccaagaagg cgctgcagtc ctactgaggc tgcagtgcgc 2100ttcgtgggtt tcccagataa aaagcataag ctgtatggtg tctactgctt cagagcatac 2160aactga 2166

[0854] TABLE LIV Nucleotide sequence alignment of 1Z1P1F1 v.1 and151P3D4 v.2 151P3D4v.1------------------------------------------------------------ 151P3D4v.2ATGTTGGAGCATACTACTAAGACATTCCCCTTAAGAGCACTGCACATAGTTGTGGAAAGC 60151P3D4v.1 ------------------------------------------------------------151P3D4v.2 ATTAGGGACCACAGTGGCCAAAAAATGAAGCAGGATAAGAAGGTGGATCTTCTTGTTCCA120 151P3D4v.1------------------------------------------------------------ 151P3D4v.2ACCAAAGTGACTGGCATCATTACACAAGGAGCTAAAGATTTTGGTCATGTACAGTTTGTT 180151P3D4v.1 ------------------------------------------------------------151P3D4v.2 GGCTCCTACAAACTGGCTTACAGCAATGATGGAGAACACTGGACTGTATACCAGGATGAA240 151P3D4v.1------------------------------------------------------------ 151P3D4v.2AAGCAAAGAAAAGATAAGGTACTGCTGGGCCGGAAGGCGCTGGTCGTAAGCTGCGAAGGC 300151P3D4v.1 ------------------------------------------------------------151P3D4v.2 ATCAACATTTCTGGCAGTTTCTGCAGAAACAAGTTGAAGTACCTGGCTTTCCTCCACAAG360 151P3D4v.1------------------------------------------------------------ 151P3D4v.2CGGATGAACACCAACCCTTCTCGACCCCCCTACCACTTCCAGCTCCCCAGCCGCATCTTC 420151P3D4V.1 ------------------------------------------------------------151P3D4v.2 TGGCGACAAGAAAAAGCACATGGTGGTTCCTGCTCCCCTCAAGGTCATGCGTCTGAAGCC480 151P3D4v.1------------------------------------------------------------ 151P3D4v.2TACAAGAAAGTTTGCCTATCTGGGGCGCCTCACGAGGTTGGCTGGAAGTACCAGGCAGTG 540151P3D4v.1 ------------------------------------------------------------151P3D4v.2 ACAGCCACCCTGCAGGAAAAGAGGAAAGAGAAAGCCGAGATCCACTACCGGAAGAATAAA600 151P3D4v.1------------------------------------------------------------ 151P3D4v.2ACAGCCACCCTGGAGGAAAAGAGGAAAGAGAAAGCCGAGATCCACTACCGGAAGAATAAA 660151P3D4v.1 ------------------------------------------------------------151P3D4v.2 ACAGAGAGTCCAGGAGGAGGCAGTCCCCGTCGCTTAGGCTTTATCTTTAAGACAATAGCG720 151P3D4v.1----------------------------------------------TTAGGCTGTA-ATT 13151P3D4v.2 CCGCTCGCCGCCACCCOCGCGACTCGGATCGGGCATCCCCGCGGCCGCACCCCGCGCGCT780                                                 *  * *     *151P3D4v.1 AGGGGATTTGGGAGGAGA--ACTTTCCTGGTGACGCTTTGCTTTTCTTCTGCT--CTTGG69 151P3D4v.2GGCTCATCTGCACACCGGCCACCTGCATTATCGGCCAGAGCCCCCGTCCCGGCGGCTTCC 840 *   ** **      *   ** * * * **     *   **    * * *    *** 151P3D4v.1TCAGAAAGT-GCCTCCTTCTTCCCAGGATCAGGACCT--CTGCCATCCAGCGCCACAA-- 124151P3D4v.2 CCAGCAGCTTGGCTGCCCCTCAGGACGCCCTGGACCCGCCCATCCTCCTGCCCCACTAGC900   ** *  * * ** *  **    * *  * *****   *   * *** ** **** *151P3D4v.1 --AGAGACATTCTGCACACACACTCACACACACACACACACACACACTCTCACACTCCC-181 151P3D4V.2TCATCGACTTACGACTCCCTCAGTCCCTACGGCCCACGGA-ACCCTCTCCCCAACCCGCG 959  *  *** * *  * * * ** ** *     * ***  * ** * *** *  ** *** 151P3D4v.1CCAGAGACAAACTTAACGTGAGG-----AGAAAGAGCGCTA--CGTTCACTTCATCTCCA 234151P3D4V.2 CCACAGCCCGAGCGGCGGCGGCGGCCTTAAGAAGCCCGCAAGACACTGTCAAGGTCAAAA1019 *** ** *  *  ** *  *        *  ***  *** *  *  *  *  * **   *151P3D4v.1 GC------TTCCAACTTAAGCAGAACTTGAGAGCATCCGAACTCCTGGATTTCAGGACAA288 151P3D4v.2GCACAATGTGCTAGCCAGGGGGAAACCCCAGAGAAAGCCAAAATCTGAAAATAACAGCTG 1079**      * * * *    *   ***   **** *  * **   *** *  * *   * 151P3D4v.1GTGAAGAAGATTCTTTGGGC-TATAAAGATGA-AGAGTCTACTTCTTCTGGTGCTGATTT 346151P3D4v.2 GTATGTAGAAAACGGCAGACCTCCTCACTTGGCAGGCTCAGGATATTGTGGTGCTCTTTG1139 **    *  *  *    * * *    *  **  **  **    * ** *******  **151P3D4v.1 CAATCTGCTGGGCTGATCATCTTTCAGACAACTATACTCTGGATCATGACAGAGCTATTC406 151P3D4v.2GAAGGCAATACA------GTCCTTGGAGGAAGGACTTGGAGGAAAACAAAAGGACAAGGA 1193 **     * *        ** **     **  *      ***  *  * **  * * 151P3D4v.1ACATCCAAGCAGAAAATGGCCCCCATCTACTTGTGGAAGCAGAGCAAGCCAAGGTGTTTT 466151P3D4v.2 A-AGGAAAGCAGAAAATGGCCCCCATCTACTTGTGGAAGCAGAOCAAGCCAAGGTGTTTT1252 * *   ******************************************************151P3D4v.1 CACACAGAGGTGGCAATGTTACACTGCCATGTAAATTTTATCGAGACCCTACAGCATTTG526 151P3D4v.2CACACAGAGGTGGCAATGTTACACTCCCATGTAAATTTTATCGAGACCCTACAGCATTTG 1312************************************************************ 151P3D4v.1GCTCAGGAATCCATAAAATCCGAATTAAGTGGACCAAGCTAACTTCGGATTACCTCAAGG 586151P3D4v.2 GCTCAGGAATCCATAAAATCCGAATTAAGTGGACCAAGCTAACTTCGGATTACCTCAAGG1372 ************************************************************151P3D4v.1 AAGTGGATGTTTTTGTTTCCATGGGATACCACAAAAAAACCTATGGAGGCTACCAGGGTA646 151P3D4v.2AAGTGGATGTTTTTGTTTCCATGGGATACCACAAAAAAACCTATGGAGGCTACCAGGGTA 1432************************************************************ 151P3D4v.1GAGTGTTTCTGAAGGGAGGCAGTGATAGTGATGCTTCTCTGGTCATCACAGACCTCACTC 706151P3D4v.2 GAGTGTTTCTGAAGGGAGGCAGTGATAGTGATGCTTCTCTGGTCATCACAGACCTCACTC1492 ************************************************************151P3D4v.1 TGGAAGATTAGGGGAGATATAAGTGTGAGGTGATTGAAGGATTAGAAGATGATACTGTTG766 151P3D4v.2TGGAAGATTATGGGAGATATAAGTGTGAGCTGATTGAAGGATTAGAAGATCATACTGTTG 1552************************************************************ 151P3D4v.1TGGTAGCACTGCACTTACAAGGTGTCGTATTCCCTTACTTTCCACGACTCGGGCGCTACA 826151P3D4v.2 TGGTAGCACTGGACTTACAAGGTCTGGTATTCCCTTACTTTCCACGACTGGGGCGCTACA1612 ************************************************************151P3D4v.1 ATCTCAATTTTCACGAGCCGCAGCAGGCGTGTCTGGACCAGGATGCTGTGATCGCCTCCT886 151P3D4v.2ATCTCAATTTTCACGAGGCGCAGCAGGCGTGTCTGGACCAGGATGCTGTGATCGCCTCCT 1672************************************************************ 151P3D4v.1TCGACCAGCTGTACGACGCCTGGCGGGGCGGGCTGGACTGGTGCAATGCCCGCTGGCTCA 946151P3D4v.2 TCGACCAGCTGTACGACGCCTGGCGGGGCGGGCTGGACTGGTGCAATGCCGGCTGGCTCA1732 ************************************************************151P3D4v.1 GTGATGGCTCTGTGCAATATCCCATCACAAAGCCCAGAGAGCCCTGTGGGGGCCAGAACA1006 151P3D4v.2GTGATGGCTCTGTGCAATATCCCATCACAAAGCCCAGAGAGCCCTGTGGGGGGCAGAACA 1792**************************************************** ******* 151P3D4v.1CAGTGCCCGGAGTCAGGAACTACGGATTTTGGGATAAAGATAAAAGCAGATATGATGTTT 1066151P3D4v.2 CAGTGCCCGGAGTCAGGAACTACCGATTTTGGGATAAAGATAAAAGCAGATATGATGTTT1852 ************************************************************151P3D4v.1 TCTGTTTTACATCCAATTTCAATGGCCGTTTTTACTATCTGATCCACCCCACCAAACTGA1126 151P3D4v.2TCTGTTTTACATCCAATTTCAATGGCCGTTTTTACTATCTGATCCACCCCACCAAACTGA 1912************************************************************ 151P3D4v.1CCTATGATGAAGCGGTGCAAGCTTGTCTCAATGATGGTGCTCAGATTGCAAAAGTGGGCC 1186151P3D4v.2 CCTATGATGAAGCGGTGCAACCTTGTCTCAATGATGGTGCTCAGATTGCAAAAGTGGGCC1972 ************************************************************151P3D4v.1 AGATATTTGCTCCCTGGAAAATTCTCGGATATCACCGCTGTGATGCGGGCTGGTTGGCGG1246 151P3D4v.2AGATATTTGCTGCCTGGAAAATTCTCGGATATGACCGCTGTGATGCGGGCTGGTTGGCGG 2032************************************************************ 151P3D4v.1ATGGCAGCGTCCGCTACCCCATCTCTAGGCCAAGAAGGCGCTGCAGTCCTACTGAGGCTG 1306151P3D4v.2 ATGGCAGCGTCCGCTACCCCATCTCTAGGCCAAGAAGGCGCTGCAGTCCTACTGACGCTG2092 ************************************************************151P3D4v.1 CAGTGCGCTTCGTGGGTTTCCCAGATAAAAAGCATAAGCTGTATGGTGTCTACTGCTTCA1366 151P3D4v.2CAGTGCGCTTCGTGGGTTTCCCAGATAAAAAGCATAAGCTGTATGGTGTCTACTGCTTCA 2152************************************************************ 151P3D4v.1GAGCATACAACTGAATGTGCCCTTAGAGCGCATCAGTTTTAAAGTCATTAAGAACATGTG 1426151P3D4v.2 GAGCATACAACTGA----------------------------------------------2166 ************** 151P3D4v.1AAAGGTGTTTTTTTTTTCCAATATGAACTCATGCAAGTTACCAAAACTGTGATAACCCTT 1486151P3D4v.2 ------------------------------------------------------------151P3D4v.1 TTTTACTTACTGTAAAGAGTCATTTTCATAAGATCAATTCATTGATTTGTTTTTTGTAAA1546 151P3D4v.2------------------------------------------------------------ 151P3D4v.1GCTATCATTCAATATATATTATAAATTAATATAAATTTAAGGCAAGCTCTATGTAAGGAG 1606151P3D4v.2 ------------------------------------------------------------151P3D4v.1 ACTTAGAGCCAAACTGTTTAAGCTGTATCATCCCAACAAAGTATCCTTTCATGAACGGGG1666 151PSD4v.2------------------------------------------------------------ 151P3D4v.1CATGCAATAGCTTAAGAATTGCTACGATTAAATTAAGGAAACTAAAGCTACTCAGAGCAA 1726151P3D4v.2 ------------------------------------------------------------151P2D4v.1 CAGGTTCCACAAGCACAAACTTTACACATTTGTACAATTTTCAAATGCACTACAATAAAC1786 151P3D4v.2------------------------------------------------------------ 151P3D4v.1AAATTAGAGCAACACATTTGAAATACAGGCTTCTTTACATAAACTGAGAGGTTATACAAA 1846151P3D4v.2 ------------------------------------------------------------151P3D4v.1 ACTCAGTTTCACAAGGGAACAATCTATACCTTTCTAAAAGTTAATATTTCAAGTCTCTAA1906 151PSD4v.2------------------------------------------------------------ 151P3D4v.1TAGGCAGAATATTTTACTCTTTAAAATCCTGCCTTTCTGACCAAAAAAAAA 1957 151P3D4v.2---------------------------------------------------

[0855] TABLE LV Amino acid sequence alignment of 121PJF1v.1 and151P3D4v.2 151P3D4v.1------------------------------------------------------------ 151P3D4v.2MLEHTTKTFPLRALHIVVESIRDNSGQKNKQDKKVDLLVPTKVTGIITQGAKDFGHVQFV 60151P3D4v.1 ------------------------------------------------------------151P3D4v.2 GSYKLAYSNDGEHWTVYQDEKQRKDKVLLGRKAVVVSCEGINISGSFCRNKLKYLAFLHK120 151P3D4v.1-------MKSLLLLVLISICWAdHLSDN-------------------------------- 21151P3D4v.2 RMNTNPSRRPYHFQVPSRIFWRQEKADGGSCCPQGHASEAYKKVCLSGAPHEVGWKYQAV180         :.  : *   * * :. :*. 151P3D4v.1---------------------------------------YT------------------- 15123D4v.2TATLEEKRKEKAEIHYRKNKQLMRLQKQAEKNMKKKIDKYTESPGCGSPRGLGFIFKTIA 240151P3D4v.1 -LDHDRAIMI--------------------------------------------------32 151P3D4v.2PLAATRATRIGHPGGRTPRAGSSAHRPPALSARAPVPAASPAAWLPLRTPWTRPSSCPTS 300 *   ** :* 151P3D4v.1------------------------------------------------------------ 151PSD4v.2SSTYDSLSPYGPRNPLPNPRHSPSGGGGLKKPARHCQGQKHNVLARGKPQRKPKSENNSW 360151P3D4v.1 ---------------------------------------QAENGPHLLVEAEQAKVPSHR53 151P3D4V.2YVENGRPADLAGSGYCGALWKAIESLEEGLGGKQKDKERKAENGPHLLVEAEQAKVFSHR 420                                        ******************** 151P3D4v.1GGNVTLPCKFYRDPTAFGSGIHKIRIKWTKLTSDYLKEVDVFVSMGYHKKTYGGYQGRVF 113151P3D4v.2 GGNVTLPCKFYRDPTAFGSGTHKIRIKWTKLTSDYLKEVDVFVSMGYNKKTYGGYQGRVF480 ************************************************************151P3D4v.1 LKGGSDSDASLVITDLTLEDYGRYKCEVIEGLEDDTVVVALDLQGVVFPYFPRLGRYNLN173 151P3D4v.2LKGGSDSDASLVITDLTLEDYGRYKCEVIEGLEDDTVVVALDLQGVVFPYFPRLGRYNLN 540************************************************************ 151P3D4v.1FHEAQQACLDQDAVIASFDQLYDAWRGGLDWCNAGWLSDGSVQYPITKPREPCGGQNTVP 233151P3D4v.2 FHEAQQACLDQDAVIASFDQLYDAWRGGLDWCNAGWLSDGSVQYPITKPREPCGGQNTVP600 ************************************************************151P3D4v.1 GVRNYGFWDkDKSRYDVFCFTSNFNGRFYYLIHPTKLTYDEAVQACLNDGAQIAKVGQIF293 151P3D4v.2GVRNYGFWDKDKSRYDVFCFTSNFNGRFYYLIHPTKLTYDEAVQACLNDGAQIAKVGQIF 660************************************************************ 151P3D4v.1AAWKILGYDRCDACWLADGSVRYPISRPRRRCSPTEAAVRFVGFPDKKHKLYGVYCFRAY 353151P3D4v.2 AAWKILGYDRCDAGWLADGSVRYPISRPRRRCSPTEAAVRPVGFPDKKNKLYGVYCFRAY720 ************************************************************151P3D4v.1 N 354 151P3D4v.2 N 721

[0856]

1 67 1 417 DNA Homo sapiens misc_feature 393 n = a, t, c, or g 1gatccacccc accaaactga cctatgatga agcggtgcaa gcttgtctca atgatggtgc 60tcagattgca aaagtgggcc agatatttgc tgcctggaaa attctcggat atgaccgctg 120tgatgcgggc tggttggcgg atggcagcgt ccgctacccc atctctaggc caagaaggcg 180ctgcagtcct actgaggctg cagtgcgctt cgtgggtttc ccagataaaa agcataagct 240gtatggtgtc tactgcttca gagcatacaa ctgaatgtgc ccttagagcg catcagtttt 300aaagtcatta agaacatgtg aaaggtgttt tttttttcca atatgaactc atgcaagtta 360ccaaaactgt gataaccctt ttttacttac tgnaaagaag tcattttcat aaagatc 417 21957 DNA Homo sapiens CDS (316)...(1380) 2 ttaggctgta attaggggatttgggaggag aactttcctg gtgacgcttt gcttttcttc 60 tgctcttggt gagaaagtgcctccttcttc ccaggatcag gacctctgcc atccagcgcc 120 acaaagagac attctgcacacacactcaca cacacacaca cacacacact ctcacactcg 180 cccagagaca aacttaaggtgaggagaaag agcgctacgt tcacttgatc tccagcttcc 240 aacttaagca gaacttgagagcatccgaac tcctggattt caggacaagt gaagaagatt 300 ctttgggcta taaag atg aagagt cta ctt ctt ctg gtg ctg att tca atc 351 Met Lys Ser Leu Leu Leu LeuVal Leu Ile Ser Ile 1 5 10 tgc tgg gct gat cat ctt tca gac aac tat actctg gat cat gac aga 399 Cys Trp Ala Asp His Leu Ser Asp Asn Tyr Thr LeuAsp His Asp Arg 15 20 25 gct att cac atc caa gca gaa aat ggc ccc cat ctactt gtg gaa gca 447 Ala Ile His Ile Gln Ala Glu Asn Gly Pro His Leu LeuVal Glu Ala 30 35 40 gag caa gcc aag gtg ttt tca cac aga ggt ggc aat gttaca ctg cca 495 Glu Gln Ala Lys Val Phe Ser His Arg Gly Gly Asn Val ThrLeu Pro 45 50 55 60 tgt aaa ttt tat cga gac cct aca gca ttt ggc tca ggaatc cat aaa 543 Cys Lys Phe Tyr Arg Asp Pro Thr Ala Phe Gly Ser Gly IleHis Lys 65 70 75 atc cga att aag tgg acc aag cta act tcg gat tac ctc aaggaa gtg 591 Ile Arg Ile Lys Trp Thr Lys Leu Thr Ser Asp Tyr Leu Lys GluVal 80 85 90 gat gtt ttt gtt tcc atg gga tac cac aaa aaa acc tat gga ggctac 639 Asp Val Phe Val Ser Met Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr95 100 105 cag ggt aga gtg ttt ctg aag gga ggc agt gat agt gat gct tctctg 687 Gln Gly Arg Val Phe Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser Leu110 115 120 gtc atc aca gac ctc act ctg gaa gat tat ggg aga tat aag tgtgag 735 Val Ile Thr Asp Leu Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu125 130 135 140 gtg att gaa gga tta gaa gat gat act gtt gtg gta gca ctggac tta 783 Val Ile Glu Gly Leu Glu Asp Asp Thr Val Val Val Ala Leu AspLeu 145 150 155 caa ggt gtg gta ttc cct tac ttt cca cga ctg ggg cgc tacaat ctc 831 Gln Gly Val Val Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr AsnLeu 160 165 170 aat ttt cac gag gcg cag cag gcg tgt ctg gac cag gat gctgtg atc 879 Asn Phe His Glu Ala Gln Gln Ala Cys Leu Asp Gln Asp Ala ValIle 175 180 185 gcc tcc ttc gac cag ctg tac gac gcc tgg cgg ggc ggg ctggac tgg 927 Ala Ser Phe Asp Gln Leu Tyr Asp Ala Trp Arg Gly Gly Leu AspTrp 190 195 200 tgc aat gcc ggc tgg ctc agt gat ggc tct gtg caa tat cccatc aca 975 Cys Asn Ala Gly Trp Leu Ser Asp Gly Ser Val Gln Tyr Pro IleThr 205 210 215 220 aag ccc aga gag ccc tgt ggg ggc cag aac aca gtg cccgga gtc agg 1023 Lys Pro Arg Glu Pro Cys Gly Gly Gln Asn Thr Val Pro GlyVal Arg 225 230 235 aac tac gga ttt tgg gat aaa gat aaa agc aga tat gatgtt ttc tgt 1071 Asn Tyr Gly Phe Trp Asp Lys Asp Lys Ser Arg Tyr Asp ValPhe Cys 240 245 250 ttt aca tcc aat ttc aat ggc cgt ttt tac tat ctg atccac ccc acc 1119 Phe Thr Ser Asn Phe Asn Gly Arg Phe Tyr Tyr Leu Ile HisPro Thr 255 260 265 aaa ctg acc tat gat gaa gcg gtg caa gct tgt ctc aatgat ggt gct 1167 Lys Leu Thr Tyr Asp Glu Ala Val Gln Ala Cys Leu Asn AspGly Ala 270 275 280 cag att gca aaa gtg ggc cag ata ttt gct gcc tgg aaaatt ctc gga 1215 Gln Ile Ala Lys Val Gly Gln Ile Phe Ala Ala Trp Lys IleLeu Gly 285 290 295 300 tat gac cgc tgt gat gcg ggc tgg ttg gcg gat ggcagc gtc cgc tac 1263 Tyr Asp Arg Cys Asp Ala Gly Trp Leu Ala Asp Gly SerVal Arg Tyr 305 310 315 ccc atc tct agg cca aga agg cgc tgc agt cct actgag gct gca gtg 1311 Pro Ile Ser Arg Pro Arg Arg Arg Cys Ser Pro Thr GluAla Ala Val 320 325 330 cgc ttc gtg ggt ttc cca gat aaa aag cat aag ctgtat ggt gtc tac 1359 Arg Phe Val Gly Phe Pro Asp Lys Lys His Lys Leu TyrGly Val Tyr 335 340 345 tgc ttc aga gca tac aac tga atgtgcccttagagcgcatc agttttaaag 1410 Cys Phe Arg Ala Tyr Asn * 350 tcattaagaacatgtgaaag gtgttttttt tttccaatat gaactcatgc aagttaccaa 1470 aactgtgataaccctttttt acttactgta aagagtcatt ttcataagat caattcattg 1530 atttgttttttgtaaagcta tcattcaata tatattataa attaatataa atttaaggga 1590 agctctatgtaaggagactt agagccaaac tgtttaagct gtatcatccc aacaaagtat 1650 cctttcatgaacggggcatg caatagctta agaattgcta ggattaaatt aaggaaagta 1710 aagctactcagagcaacagg ttccacaagc acaaacttta cacatttgta caattttgaa 1770 atgcactacaataaacaaat tagagcaaca catttgaaat acaggcttct ttacataaac 1830 tgagaggttatacaaaactc agtttcacaa gggaacaatc tatacctttc taaaagttaa 1890 tatttcaagtctctaatagg cagaatattt tactctttaa aatcctgcct ttctgaccaa 1950 aaaaaaa 19573 354 PRT Homo sapiens 3 Met Lys Ser Leu Leu Leu Leu Val Leu Ile Ser IleCys Trp Ala Asp 1 5 10 15 His Leu Ser Asp Asn Tyr Thr Leu Asp His AspArg Ala Ile His Ile 20 25 30 Gln Ala Glu Asn Gly Pro His Leu Leu Val GluAla Glu Gln Ala Lys 35 40 45 Val Phe Ser His Arg Gly Gly Asn Val Thr LeuPro Cys Lys Phe Tyr 50 55 60 Arg Asp Pro Thr Ala Phe Gly Ser Gly Ile HisLys Ile Arg Ile Lys 65 70 75 80 Trp Thr Lys Leu Thr Ser Asp Tyr Leu LysGlu Val Asp Val Phe Val 85 90 95 Ser Met Gly Tyr His Lys Lys Thr Tyr GlyGly Tyr Gln Gly Arg Val 100 105 110 Phe Leu Lys Gly Gly Ser Asp Ser AspAla Ser Leu Val Ile Thr Asp 115 120 125 Leu Thr Leu Glu Asp Tyr Gly ArgTyr Lys Cys Glu Val Ile Glu Gly 130 135 140 Leu Glu Asp Asp Thr Val ValVal Ala Leu Asp Leu Gln Gly Val Val 145 150 155 160 Phe Pro Tyr Phe ProArg Leu Gly Arg Tyr Asn Leu Asn Phe His Glu 165 170 175 Ala Gln Gln AlaCys Leu Asp Gln Asp Ala Val Ile Ala Ser Phe Asp 180 185 190 Gln Leu TyrAsp Ala Trp Arg Gly Gly Leu Asp Trp Cys Asn Ala Gly 195 200 205 Trp LeuSer Asp Gly Ser Val Gln Tyr Pro Ile Thr Lys Pro Arg Glu 210 215 220 ProCys Gly Gly Gln Asn Thr Val Pro Gly Val Arg Asn Tyr Gly Phe 225 230 235240 Trp Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys Phe Thr Ser Asn 245250 255 Phe Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr Lys Leu Thr Tyr260 265 270 Asp Glu Ala Val Gln Ala Cys Leu Asn Asp Gly Ala Gln Ile AlaLys 275 280 285 Val Gly Gln Ile Phe Ala Ala Trp Lys Ile Leu Gly Tyr AspArg Cys 290 295 300 Asp Ala Gly Trp Leu Ala Asp Gly Ser Val Arg Tyr ProIle Ser Arg 305 310 315 320 Pro Arg Arg Arg Cys Ser Pro Thr Glu Ala AlaVal Arg Phe Val Gly 325 330 335 Phe Pro Asp Lys Lys His Lys Leu Tyr GlyVal Tyr Cys Phe Arg Ala 340 345 350 Tyr Asn 4 2166 DNA Homo sapiens CDS(1)...(2166) 4 atg ttg gag cat act act aag aca ttc ccc tta aga gca ctgcac ata 48 Met Leu Glu His Thr Thr Lys Thr Phe Pro Leu Arg Ala Leu HisIle 1 5 10 15 gtt gtg gaa agc att agg gac cac agt ggc caa aaa atg aagcag gat 96 Val Val Glu Ser Ile Arg Asp His Ser Gly Gln Lys Met Lys GlnAsp 20 25 30 aag aag gtg gat ctt ctt gtt cca acc aaa gtg act ggc atc attaca 144 Lys Lys Val Asp Leu Leu Val Pro Thr Lys Val Thr Gly Ile Ile Thr35 40 45 caa gga gct aaa gat ttt ggt cat gta cag ttt gtt ggc tcc tac aaa192 Gln Gly Ala Lys Asp Phe Gly His Val Gln Phe Val Gly Ser Tyr Lys 5055 60 ctg gct tac agc aat gat gga gaa cac tgg act gta tac cag gat gaa240 Leu Ala Tyr Ser Asn Asp Gly Glu His Trp Thr Val Tyr Gln Asp Glu 6570 75 80 aag caa aga aaa gat aag gta ctg ctg ggc cgg aag gcg gtg gtc gta288 Lys Gln Arg Lys Asp Lys Val Leu Leu Gly Arg Lys Ala Val Val Val 8590 95 agc tgc gaa ggc atc aac att tct ggc agt ttc tgc aga aac aag ttg336 Ser Cys Glu Gly Ile Asn Ile Ser Gly Ser Phe Cys Arg Asn Lys Leu 100105 110 aag tac ctg gct ttc ctc cac aag cgg atg aac acc aac cct tct cga384 Lys Tyr Leu Ala Phe Leu His Lys Arg Met Asn Thr Asn Pro Ser Arg 115120 125 cgc ccc tac cac ttc cag gtc ccc agc cgc atc ttc tgg cga caa gaa432 Arg Pro Tyr His Phe Gln Val Pro Ser Arg Ile Phe Trp Arg Gln Glu 130135 140 aaa gca gat ggt ggt tcc tgc tgc cct caa ggt cat gcg tct gaa gcc480 Lys Ala Asp Gly Gly Ser Cys Cys Pro Gln Gly His Ala Ser Glu Ala 145150 155 160 tac aag aaa gtt tgc cta tct ggg gcg cct cac gag gtt ggc tggaag 528 Tyr Lys Lys Val Cys Leu Ser Gly Ala Pro His Glu Val Gly Trp Lys165 170 175 tac cag gca gtg aca gcc acc ctg gag gaa aag agg aaa gag aaagcc 576 Tyr Gln Ala Val Thr Ala Thr Leu Glu Glu Lys Arg Lys Glu Lys Ala180 185 190 gag atc cac tac cgg aag aat aaa cag ctc atg agg cta cag aaacag 624 Glu Ile His Tyr Arg Lys Asn Lys Gln Leu Met Arg Leu Gln Lys Gln195 200 205 gcc gag aag aac atg aag aag aaa att gac aaa tac aca gag agtcca 672 Ala Glu Lys Asn Met Lys Lys Lys Ile Asp Lys Tyr Thr Glu Ser Pro210 215 220 gga gga ggc agt ccc cgt ggc tta ggc ttt atc ttt aag aca atagcg 720 Gly Gly Gly Ser Pro Arg Gly Leu Gly Phe Ile Phe Lys Thr Ile Ala225 230 235 240 ccg ctc gcc gcc acc cgc gcg act cgg atc ggg cat ccc ggcggc cgc 768 Pro Leu Ala Ala Thr Arg Ala Thr Arg Ile Gly His Pro Gly GlyArg 245 250 255 acc ccg cgc gct ggc tca tct gca cac cgg cca cct gca ttgtcg gcc 816 Thr Pro Arg Ala Gly Ser Ser Ala His Arg Pro Pro Ala Leu SerAla 260 265 270 aga gcc ccc gtc ccg gcg gct tcc cca gca gct tgg ctg cccctc agg 864 Arg Ala Pro Val Pro Ala Ala Ser Pro Ala Ala Trp Leu Pro LeuArg 275 280 285 acg ccc tgg acc cgc cca tcc tcc tgc ccc act agc tca tcgact tac 912 Thr Pro Trp Thr Arg Pro Ser Ser Cys Pro Thr Ser Ser Ser ThrTyr 290 295 300 gac tcc ctc agt ccc tac ggc cca cgg aac cct ctc ccc aacccg cgc 960 Asp Ser Leu Ser Pro Tyr Gly Pro Arg Asn Pro Leu Pro Asn ProArg 305 310 315 320 cac agc ccg agc ggc ggc ggc ggc ctt aag aag ccc gcaaga cac tgt 1008 His Ser Pro Ser Gly Gly Gly Gly Leu Lys Lys Pro Ala ArgHis Cys 325 330 335 caa ggt caa aag cac aat gtg cta gcc agg ggg aaa ccccag aga aag 1056 Gln Gly Gln Lys His Asn Val Leu Ala Arg Gly Lys Pro GlnArg Lys 340 345 350 cca aaa tct gaa aat aac agc tgg tat gta gaa aac ggcaga cct gct 1104 Pro Lys Ser Glu Asn Asn Ser Trp Tyr Val Glu Asn Gly ArgPro Ala 355 360 365 gac ttg gca ggc tca gga tat tgt ggt gct ctt tgg aaggca ata gag 1152 Asp Leu Ala Gly Ser Gly Tyr Cys Gly Ala Leu Trp Lys AlaIle Glu 370 375 380 tcc ttg gag gaa gga ctt gga gga aaa caa aag gac aaggaa agg aaa 1200 Ser Leu Glu Glu Gly Leu Gly Gly Lys Gln Lys Asp Lys GluArg Lys 385 390 395 400 gca gaa aat ggc ccc cat cta ctt gtg gaa gca gagcaa gcc aag gtg 1248 Ala Glu Asn Gly Pro His Leu Leu Val Glu Ala Glu GlnAla Lys Val 405 410 415 ttt tca cac aga ggt ggc aat gtt aca ctg cca tgtaaa ttt tat cga 1296 Phe Ser His Arg Gly Gly Asn Val Thr Leu Pro Cys LysPhe Tyr Arg 420 425 430 gac cct aca gca ttt ggc tca gga atc cat aaa atccga att aag tgg 1344 Asp Pro Thr Ala Phe Gly Ser Gly Ile His Lys Ile ArgIle Lys Trp 435 440 445 acc aag cta act tcg gat tac ctc aag gaa gtg gatgtt ttt gtt tcc 1392 Thr Lys Leu Thr Ser Asp Tyr Leu Lys Glu Val Asp ValPhe Val Ser 450 455 460 atg gga tac cac aaa aaa acc tat gga ggc tac cagggt aga gtg ttt 1440 Met Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr Gln GlyArg Val Phe 465 470 475 480 ctg aag gga ggc agt gat agt gat gct tct ctggtc atc aca gac ctc 1488 Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser Leu ValIle Thr Asp Leu 485 490 495 act ctg gaa gat tat ggg aga tat aag tgt gaggtg att gaa gga tta 1536 Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu ValIle Glu Gly Leu 500 505 510 gaa gat gat act gtt gtg gta gca ctg gac ttacaa ggt gtg gta ttc 1584 Glu Asp Asp Thr Val Val Val Ala Leu Asp Leu GlnGly Val Val Phe 515 520 525 cct tac ttt cca cga ctg ggg cgc tac aat ctcaat ttt cac gag gcg 1632 Pro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu AsnPhe His Glu Ala 530 535 540 cag cag gcg tgt ctg gac cag gat gct gtg atcgcc tcc ttc gac cag 1680 Gln Gln Ala Cys Leu Asp Gln Asp Ala Val Ile AlaSer Phe Asp Gln 545 550 555 560 ctg tac gac gcc tgg cgg ggc ggg ctg gactgg tgc aat gcc ggc tgg 1728 Leu Tyr Asp Ala Trp Arg Gly Gly Leu Asp TrpCys Asn Ala Gly Trp 565 570 575 ctc agt gat ggc tct gtg caa tat ccc atcaca aag ccc aga gag ccc 1776 Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile ThrLys Pro Arg Glu Pro 580 585 590 tgt ggg ggg cag aac aca gtg ccc gga gtcagg aac tac gga ttt tgg 1824 Cys Gly Gly Gln Asn Thr Val Pro Gly Val ArgAsn Tyr Gly Phe Trp 595 600 605 gat aaa gat aaa agc aga tat gat gtt ttctgt ttt aca tcc aat ttc 1872 Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe CysPhe Thr Ser Asn Phe 610 615 620 aat ggc cgt ttt tac tat ctg atc cac cccacc aaa ctg acc tat gat 1920 Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro ThrLys Leu Thr Tyr Asp 625 630 635 640 gaa gcg gtg caa gct tgt ctc aat gatggt gct cag att gca aaa gtg 1968 Glu Ala Val Gln Ala Cys Leu Asn Asp GlyAla Gln Ile Ala Lys Val 645 650 655 ggc cag ata ttt gct gcc tgg aaa attctc gga tat gac cgc tgt gat 2016 Gly Gln Ile Phe Ala Ala Trp Lys Ile LeuGly Tyr Asp Arg Cys Asp 660 665 670 gcg ggc tgg ttg gcg gat ggc agc gtccgc tac ccc atc tct agg cca 2064 Ala Gly Trp Leu Ala Asp Gly Ser Val ArgTyr Pro Ile Ser Arg Pro 675 680 685 aga agg cgc tgc agt cct act gag gctgca gtg cgc ttc gtg ggt ttc 2112 Arg Arg Arg Cys Ser Pro Thr Glu Ala AlaVal Arg Phe Val Gly Phe 690 695 700 cca gat aaa aag cat aag ctg tat ggtgtc tac tgc ttc aga gca tac 2160 Pro Asp Lys Lys His Lys Leu Tyr Gly ValTyr Cys Phe Arg Ala Tyr 705 710 715 720 aac tga 2166 Asn * 5 721 PRTHomo sapiens 5 Met Leu Glu His Thr Thr Lys Thr Phe Pro Leu Arg Ala LeuHis Ile 1 5 10 15 Val Val Glu Ser Ile Arg Asp His Ser Gly Gln Lys MetLys Gln Asp 20 25 30 Lys Lys Val Asp Leu Leu Val Pro Thr Lys Val Thr GlyIle Ile Thr 35 40 45 Gln Gly Ala Lys Asp Phe Gly His Val Gln Phe Val GlySer Tyr Lys 50 55 60 Leu Ala Tyr Ser Asn Asp Gly Glu His Trp Thr Val TyrGln Asp Glu 65 70 75 80 Lys Gln Arg Lys Asp Lys Val Leu Leu Gly Arg LysAla Val Val Val 85 90 95 Ser Cys Glu Gly Ile Asn Ile Ser Gly Ser Phe CysArg Asn Lys Leu 100 105 110 Lys Tyr Leu Ala Phe Leu His Lys Arg Met AsnThr Asn Pro Ser Arg 115 120 125 Arg Pro Tyr His Phe Gln Val Pro Ser ArgIle Phe Trp Arg Gln Glu 130 135 140 Lys Ala Asp Gly Gly Ser Cys Cys ProGln Gly His Ala Ser Glu Ala 145 150 155 160 Tyr Lys Lys Val Cys Leu SerGly Ala Pro His Glu Val Gly Trp Lys 165 170 175 Tyr Gln Ala Val Thr AlaThr Leu Glu Glu Lys Arg Lys Glu Lys Ala 180 185 190 Glu Ile His Tyr ArgLys Asn Lys Gln Leu Met Arg Leu Gln Lys Gln 195 200 205 Ala Glu Lys AsnMet Lys Lys Lys Ile Asp Lys Tyr Thr Glu Ser Pro 210 215 220 Gly Gly GlySer Pro Arg Gly Leu Gly Phe Ile Phe Lys Thr Ile Ala 225 230 235 240 ProLeu Ala Ala Thr Arg Ala Thr Arg Ile Gly His Pro Gly Gly Arg 245 250 255Thr Pro Arg Ala Gly Ser Ser Ala His Arg Pro Pro Ala Leu Ser Ala 260 265270 Arg Ala Pro Val Pro Ala Ala Ser Pro Ala Ala Trp Leu Pro Leu Arg 275280 285 Thr Pro Trp Thr Arg Pro Ser Ser Cys Pro Thr Ser Ser Ser Thr Tyr290 295 300 Asp Ser Leu Ser Pro Tyr Gly Pro Arg Asn Pro Leu Pro Asn ProArg 305 310 315 320 His Ser Pro Ser Gly Gly Gly Gly Leu Lys Lys Pro AlaArg His Cys 325 330 335 Gln Gly Gln Lys His Asn Val Leu Ala Arg Gly LysPro Gln Arg Lys 340 345 350 Pro Lys Ser Glu Asn Asn Ser Trp Tyr Val GluAsn Gly Arg Pro Ala 355 360 365 Asp Leu Ala Gly Ser Gly Tyr Cys Gly AlaLeu Trp Lys Ala Ile Glu 370 375 380 Ser Leu Glu Glu Gly Leu Gly Gly LysGln Lys Asp Lys Glu Arg Lys 385 390 395 400 Ala Glu Asn Gly Pro His LeuLeu Val Glu Ala Glu Gln Ala Lys Val 405 410 415 Phe Ser His Arg Gly GlyAsn Val Thr Leu Pro Cys Lys Phe Tyr Arg 420 425 430 Asp Pro Thr Ala PheGly Ser Gly Ile His Lys Ile Arg Ile Lys Trp 435 440 445 Thr Lys Leu ThrSer Asp Tyr Leu Lys Glu Val Asp Val Phe Val Ser 450 455 460 Met Gly TyrHis Lys Lys Thr Tyr Gly Gly Tyr Gln Gly Arg Val Phe 465 470 475 480 LeuLys Gly Gly Ser Asp Ser Asp Ala Ser Leu Val Ile Thr Asp Leu 485 490 495Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu Val Ile Glu Gly Leu 500 505510 Glu Asp Asp Thr Val Val Val Ala Leu Asp Leu Gln Gly Val Val Phe 515520 525 Pro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu Asn Phe His Glu Ala530 535 540 Gln Gln Ala Cys Leu Asp Gln Asp Ala Val Ile Ala Ser Phe AspGln 545 550 555 560 Leu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp Cys AsnAla Gly Trp 565 570 575 Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr LysPro Arg Glu Pro 580 585 590 Cys Gly Gly Gln Asn Thr Val Pro Gly Val ArgAsn Tyr Gly Phe Trp 595 600 605 Asp Lys Asp Lys Ser Arg Tyr Asp Val PheCys Phe Thr Ser Asn Phe 610 615 620 Asn Gly Arg Phe Tyr Tyr Leu Ile HisPro Thr Lys Leu Thr Tyr Asp 625 630 635 640 Glu Ala Val Gln Ala Cys LeuAsn Asp Gly Ala Gln Ile Ala Lys Val 645 650 655 Gly Gln Ile Phe Ala AlaTrp Lys Ile Leu Gly Tyr Asp Arg Cys Asp 660 665 670 Ala Gly Trp Leu AlaAsp Gly Ser Val Arg Tyr Pro Ile Ser Arg Pro 675 680 685 Arg Arg Arg CysSer Pro Thr Glu Ala Ala Val Arg Phe Val Gly Phe 690 695 700 Pro Asp LysLys His Lys Leu Tyr Gly Val Tyr Cys Phe Arg Ala Tyr 705 710 715 720 Asn6 1957 DNA Homo sapiens CDS (316)...(1380) 6 ttaggctgta attaggggatttgggaggag aactttcctg gtgacgcttt gcttttcttc 60 tgctcttggt gagaaagtgcctccttcttc ccaggatcag gacctctgcc atccagcgcc 120 acaaagagac attctgcacacacactcaca cacgcacaca cacacacact ctcacactcg 180 cccagagaca aacttaaggtgaggagaaag agcgctacgt tcacttgatc tccagcttcc 240 aacttaagca gaacttgagagcatccgaac tcctggattt caggacaagt gaagaagatt 300 ctttgggcta taaag atg aagagt cta ctt ctt ctg gtg ctg att tca atc 351 Met Lys Ser Leu Leu Leu LeuVal Leu Ile Ser Ile 1 5 10 tgc tgg gct gat cat ctt tca gac aac tat actctg gat cat gac aga 399 Cys Trp Ala Asp His Leu Ser Asp Asn Tyr Thr LeuAsp His Asp Arg 15 20 25 gct att cac atc caa gca gaa aat ggc ccc cat ctactt gtg gaa gca 447 Ala Ile His Ile Gln Ala Glu Asn Gly Pro His Leu LeuVal Glu Ala 30 35 40 gag caa gcc aag gtg ttt tca cac aga ggt ggc aat gttaca ctg cca 495 Glu Gln Ala Lys Val Phe Ser His Arg Gly Gly Asn Val ThrLeu Pro 45 50 55 60 tgt aaa ttt tat cga gac cct aca gca ttt ggc tca ggaatc cat aaa 543 Cys Lys Phe Tyr Arg Asp Pro Thr Ala Phe Gly Ser Gly IleHis Lys 65 70 75 atc cga att aag tgg acc aag cta act tcg gat tac ctc aaggaa gtg 591 Ile Arg Ile Lys Trp Thr Lys Leu Thr Ser Asp Tyr Leu Lys GluVal 80 85 90 gat gtt ttt gtt tcc atg gga tac cac aaa aaa acc tat gga ggctac 639 Asp Val Phe Val Ser Met Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr95 100 105 cag ggt aga gtg ttt ctg aag gga ggc agt gat agt gat gct tctctg 687 Gln Gly Arg Val Phe Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser Leu110 115 120 gtc atc aca gac ctc act ctg gaa gat tat ggg aga tat aag tgtgag 735 Val Ile Thr Asp Leu Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu125 130 135 140 gtg att gaa gga tta gaa gat gat act gtt gtg gta gca ctggac tta 783 Val Ile Glu Gly Leu Glu Asp Asp Thr Val Val Val Ala Leu AspLeu 145 150 155 caa ggt gtg gta ttc cct tac ttt cca cga ctg ggg cgc tacaat ctc 831 Gln Gly Val Val Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr AsnLeu 160 165 170 aat ttt cac gag gcg cag cag gcg tgt ctg gac cag gat gctgtg atc 879 Asn Phe His Glu Ala Gln Gln Ala Cys Leu Asp Gln Asp Ala ValIle 175 180 185 gcc tcc ttc gac cag ctg tac gac gcc tgg cgg ggc ggg ctggac tgg 927 Ala Ser Phe Asp Gln Leu Tyr Asp Ala Trp Arg Gly Gly Leu AspTrp 190 195 200 tgc aat gcc ggc tgg ctc agt gat ggc tct gtg caa tat cccatc aca 975 Cys Asn Ala Gly Trp Leu Ser Asp Gly Ser Val Gln Tyr Pro IleThr 205 210 215 220 aag ccc aga gag ccc tgt ggg ggc cag aac aca gtg cccgga gtc agg 1023 Lys Pro Arg Glu Pro Cys Gly Gly Gln Asn Thr Val Pro GlyVal Arg 225 230 235 aac tac gga ttt tgg gat aaa gat aaa agc aga tat gatgtt ttc tgt 1071 Asn Tyr Gly Phe Trp Asp Lys Asp Lys Ser Arg Tyr Asp ValPhe Cys 240 245 250 ttt aca tcc aat ttc aat ggc cgt ttt tac tat ctg atccac ccc acc 1119 Phe Thr Ser Asn Phe Asn Gly Arg Phe Tyr Tyr Leu Ile HisPro Thr 255 260 265 aaa ctg acc tat gat gaa gcg gtg caa gct tgt ctc aatgat ggt gct 1167 Lys Leu Thr Tyr Asp Glu Ala Val Gln Ala Cys Leu Asn AspGly Ala 270 275 280 cag att gca aaa gtg ggc cag ata ttt gct gcc tgg aaaatt ctc gga 1215 Gln Ile Ala Lys Val Gly Gln Ile Phe Ala Ala Trp Lys IleLeu Gly 285 290 295 300 tat gac cgc tgt gat gcg ggc tgg ttg gcg gat ggcagc gtc cgc tac 1263 Tyr Asp Arg Cys Asp Ala Gly Trp Leu Ala Asp Gly SerVal Arg Tyr 305 310 315 ccc atc tct agg cca aga agg cgc tgc agt cct actgag gct gca gtg 1311 Pro Ile Ser Arg Pro Arg Arg Arg Cys Ser Pro Thr GluAla Ala Val 320 325 330 cgc ttc gtg ggt ttc cca gat aaa aag cat aag ctgtat ggt gtc tac 1359 Arg Phe Val Gly Phe Pro Asp Lys Lys His Lys Leu TyrGly Val Tyr 335 340 345 tgc ttc aga gca tac aac tga atgtgcccttagagcgcatc agttttaaag 1410 Cys Phe Arg Ala Tyr Asn * 350 tcattaagaacatgtgaaag gtgttttttt tttccaatat gaactcatgc aagttaccaa 1470 aactgtgataaccctttttt acttactgta aagagtcatt ttcataagat caattcattg 1530 atttgttttttgtaaagcta tcattcaata tatattataa attaatataa atttaaggga 1590 agctctatgtaaggagactt agagccaaac tgtttaagct gtatcatccc aacaaagtat 1650 cctttcatgaacggggcatg caatagctta agaattgcta ggattaaatt aaggaaagta 1710 aagctactcagagcaacagg ttccacaagc acaaacttta cacatttgta caattttgaa 1770 atgcactacaataaacaaat tagagcaaca catttgaaat acaggcttct ttacataaac 1830 tgagaggttatacaaaactc agtttcacaa gggaacaatc tatacctttc taaaagttaa 1890 tatttcaagtctctaatagg cagaatattt tactctttaa aatcctgcct ttctgaccaa 1950 aaaaaaa 19577 354 PRT Homo sapiens 7 Met Lys Ser Leu Leu Leu Leu Val Leu Ile Ser IleCys Trp Ala Asp 1 5 10 15 His Leu Ser Asp Asn Tyr Thr Leu Asp His AspArg Ala Ile His Ile 20 25 30 Gln Ala Glu Asn Gly Pro His Leu Leu Val GluAla Glu Gln Ala Lys 35 40 45 Val Phe Ser His Arg Gly Gly Asn Val Thr LeuPro Cys Lys Phe Tyr 50 55 60 Arg Asp Pro Thr Ala Phe Gly Ser Gly Ile HisLys Ile Arg Ile Lys 65 70 75 80 Trp Thr Lys Leu Thr Ser Asp Tyr Leu LysGlu Val Asp Val Phe Val 85 90 95 Ser Met Gly Tyr His Lys Lys Thr Tyr GlyGly Tyr Gln Gly Arg Val 100 105 110 Phe Leu Lys Gly Gly Ser Asp Ser AspAla Ser Leu Val Ile Thr Asp 115 120 125 Leu Thr Leu Glu Asp Tyr Gly ArgTyr Lys Cys Glu Val Ile Glu Gly 130 135 140 Leu Glu Asp Asp Thr Val ValVal Ala Leu Asp Leu Gln Gly Val Val 145 150 155 160 Phe Pro Tyr Phe ProArg Leu Gly Arg Tyr Asn Leu Asn Phe His Glu 165 170 175 Ala Gln Gln AlaCys Leu Asp Gln Asp Ala Val Ile Ala Ser Phe Asp 180 185 190 Gln Leu TyrAsp Ala Trp Arg Gly Gly Leu Asp Trp Cys Asn Ala Gly 195 200 205 Trp LeuSer Asp Gly Ser Val Gln Tyr Pro Ile Thr Lys Pro Arg Glu 210 215 220 ProCys Gly Gly Gln Asn Thr Val Pro Gly Val Arg Asn Tyr Gly Phe 225 230 235240 Trp Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys Phe Thr Ser Asn 245250 255 Phe Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr Lys Leu Thr Tyr260 265 270 Asp Glu Ala Val Gln Ala Cys Leu Asn Asp Gly Ala Gln Ile AlaLys 275 280 285 Val Gly Gln Ile Phe Ala Ala Trp Lys Ile Leu Gly Tyr AspArg Cys 290 295 300 Asp Ala Gly Trp Leu Ala Asp Gly Ser Val Arg Tyr ProIle Ser Arg 305 310 315 320 Pro Arg Arg Arg Cys Ser Pro Thr Glu Ala AlaVal Arg Phe Val Gly 325 330 335 Phe Pro Asp Lys Lys His Lys Leu Tyr GlyVal Tyr Cys Phe Arg Ala 340 345 350 Tyr Asn 8 1957 DNA Homo sapiens CDS(316)...(1380) 8 ttaggctgta attaggggat ttgggaggag aactttcctg gtgacgctttgcttttcttc 60 tgctcttggt gagaaagtgc ctccttcttc ccaggatcag gacctctgccatccagcgcc 120 acaaagagac attctgcaca cacactcaca cacacacaca cacacacactctcacactcg 180 cccagagaca aacttaaggt gaggagaaag agcgctaggt tcacttgatctccagcttcc 240 aacttaagca gaacttgaga gcatccgaac tcctggattt caggacaagtgaagaagatt 300 ctttgggcta taaag atg aag agt cta ctt ctt ctg gtg ctg atttca atc 351 Met Lys Ser Leu Leu Leu Leu Val Leu Ile Ser Ile 1 5 10 tgctgg gct gat cat ctt tca gac aac tat act ctg gat cat gac aga 399 Cys TrpAla Asp His Leu Ser Asp Asn Tyr Thr Leu Asp His Asp Arg 15 20 25 gct attcac atc caa gca gaa aat ggc ccc cat cta ctt gtg gaa gca 447 Ala Ile HisIle Gln Ala Glu Asn Gly Pro His Leu Leu Val Glu Ala 30 35 40 gag caa gccaag gtg ttt tca cac aga ggt ggc aat gtt aca ctg cca 495 Glu Gln Ala LysVal Phe Ser His Arg Gly Gly Asn Val Thr Leu Pro 45 50 55 60 tgt aaa ttttat cga gac cct aca gca ttt ggc tca gga atc cat aaa 543 Cys Lys Phe TyrArg Asp Pro Thr Ala Phe Gly Ser Gly Ile His Lys 65 70 75 atc cga att aagtgg acc aag cta act tcg gat tac ctc aag gaa gtg 591 Ile Arg Ile Lys TrpThr Lys Leu Thr Ser Asp Tyr Leu Lys Glu Val 80 85 90 gat gtt ttt gtt tccatg gga tac cac aaa aaa acc tat gga ggc tac 639 Asp Val Phe Val Ser MetGly Tyr His Lys Lys Thr Tyr Gly Gly Tyr 95 100 105 cag ggt aga gtg tttctg aag gga ggc agt gat agt gat gct tct ctg 687 Gln Gly Arg Val Phe LeuLys Gly Gly Ser Asp Ser Asp Ala Ser Leu 110 115 120 gtc atc aca gac ctcact ctg gaa gat tat ggg aga tat aag tgt gag 735 Val Ile Thr Asp Leu ThrLeu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu 125 130 135 140 gtg att gaa ggatta gaa gat gat act gtt gtg gta gca ctg gac tta 783 Val Ile Glu Gly LeuGlu Asp Asp Thr Val Val Val Ala Leu Asp Leu 145 150 155 caa ggt gtg gtattc cct tac ttt cca cga ctg ggg cgc tac aat ctc 831 Gln Gly Val Val PhePro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu 160 165 170 aat ttt cac gaggcg cag cag gcg tgt ctg gac cag gat gct gtg atc 879 Asn Phe His Glu AlaGln Gln Ala Cys Leu Asp Gln Asp Ala Val Ile 175 180 185 gcc tcc ttc gaccag ctg tac gac gcc tgg cgg ggc ggg ctg gac tgg 927 Ala Ser Phe Asp GlnLeu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp 190 195 200 tgc aat gcc ggctgg ctc agt gat ggc tct gtg caa tat ccc atc aca 975 Cys Asn Ala Gly TrpLeu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr 205 210 215 220 aag ccc agagag ccc tgt ggg ggc cag aac aca gtg ccc gga gtc agg 1023 Lys Pro Arg GluPro Cys Gly Gly Gln Asn Thr Val Pro Gly Val Arg 225 230 235 aac tac ggattt tgg gat aaa gat aaa agc aga tat gat gtt ttc tgt 1071 Asn Tyr Gly PheTrp Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys 240 245 250 ttt aca tccaat ttc aat ggc cgt ttt tac tat ctg atc cac ccc acc 1119 Phe Thr Ser AsnPhe Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr 255 260 265 aaa ctg acctat gat gaa gcg gtg caa gct tgt ctc aat gat ggt gct 1167 Lys Leu Thr TyrAsp Glu Ala Val Gln Ala Cys Leu Asn Asp Gly Ala 270 275 280 cag att gcaaaa gtg ggc cag ata ttt gct gcc tgg aaa att ctc gga 1215 Gln Ile Ala LysVal Gly Gln Ile Phe Ala Ala Trp Lys Ile Leu Gly 285 290 295 300 tat gaccgc tgt gat gcg ggc tgg ttg gcg gat ggc agc gtc cgc tac 1263 Tyr Asp ArgCys Asp Ala Gly Trp Leu Ala Asp Gly Ser Val Arg Tyr 305 310 315 ccc atctct agg cca aga agg cgc tgc agt cct act gag gct gca gtg 1311 Pro Ile SerArg Pro Arg Arg Arg Cys Ser Pro Thr Glu Ala Ala Val 320 325 330 cgc ttcgtg ggt ttc cca gat aaa aag cat aag ctg tat ggt gtc tac 1359 Arg Phe ValGly Phe Pro Asp Lys Lys His Lys Leu Tyr Gly Val Tyr 335 340 345 tgc ttcaga gca tac aac tga atgtgccctt agagcgcatc agttttaaag 1410 Cys Phe ArgAla Tyr Asn * 350 tcattaagaa catgtgaaag gtgttttttt tttccaatat gaactcatgcaagttaccaa 1470 aactgtgata accctttttt acttactgta aagagtcatt ttcataagatcaattcattg 1530 atttgttttt tgtaaagcta tcattcaata tatattataa attaatataaatttaaggga 1590 agctctatgt aaggagactt agagccaaac tgtttaagct gtatcatcccaacaaagtat 1650 cctttcatga acggggcatg caatagctta agaattgcta ggattaaattaaggaaagta 1710 aagctactca gagcaacagg ttccacaagc acaaacttta cacatttgtacaattttgaa 1770 atgcactaca ataaacaaat tagagcaaca catttgaaat acaggcttctttacataaac 1830 tgagaggtta tacaaaactc agtttcacaa gggaacaatc tatacctttctaaaagttaa 1890 tatttcaagt ctctaatagg cagaatattt tactctttaa aatcctgcctttctgaccaa 1950 aaaaaaa 1957 9 354 PRT Homo sapiens 9 Met Lys Ser LeuLeu Leu Leu Val Leu Ile Ser Ile Cys Trp Ala Asp 1 5 10 15 His Leu SerAsp Asn Tyr Thr Leu Asp His Asp Arg Ala Ile His Ile 20 25 30 Gln Ala GluAsn Gly Pro His Leu Leu Val Glu Ala Glu Gln Ala Lys 35 40 45 Val Phe SerHis Arg Gly Gly Asn Val Thr Leu Pro Cys Lys Phe Tyr 50 55 60 Arg Asp ProThr Ala Phe Gly Ser Gly Ile His Lys Ile Arg Ile Lys 65 70 75 80 Trp ThrLys Leu Thr Ser Asp Tyr Leu Lys Glu Val Asp Val Phe Val 85 90 95 Ser MetGly Tyr His Lys Lys Thr Tyr Gly Gly Tyr Gln Gly Arg Val 100 105 110 PheLeu Lys Gly Gly Ser Asp Ser Asp Ala Ser Leu Val Ile Thr Asp 115 120 125Leu Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu Val Ile Glu Gly 130 135140 Leu Glu Asp Asp Thr Val Val Val Ala Leu Asp Leu Gln Gly Val Val 145150 155 160 Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu Asn Phe HisGlu 165 170 175 Ala Gln Gln Ala Cys Leu Asp Gln Asp Ala Val Ile Ala SerPhe Asp 180 185 190 Gln Leu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp CysAsn Ala Gly 195 200 205 Trp Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile ThrLys Pro Arg Glu 210 215 220 Pro Cys Gly Gly Gln Asn Thr Val Pro Gly ValArg Asn Tyr Gly Phe 225 230 235 240 Trp Asp Lys Asp Lys Ser Arg Tyr AspVal Phe Cys Phe Thr Ser Asn 245 250 255 Phe Asn Gly Arg Phe Tyr Tyr LeuIle His Pro Thr Lys Leu Thr Tyr 260 265 270 Asp Glu Ala Val Gln Ala CysLeu Asn Asp Gly Ala Gln Ile Ala Lys 275 280 285 Val Gly Gln Ile Phe AlaAla Trp Lys Ile Leu Gly Tyr Asp Arg Cys 290 295 300 Asp Ala Gly Trp LeuAla Asp Gly Ser Val Arg Tyr Pro Ile Ser Arg 305 310 315 320 Pro Arg ArgArg Cys Ser Pro Thr Glu Ala Ala Val Arg Phe Val Gly 325 330 335 Phe ProAsp Lys Lys His Lys Leu Tyr Gly Val Tyr Cys Phe Arg Ala 340 345 350 TyrAsn 10 1957 DNA Homo sapiens CDS (316)...(1380) 10 ttaggctgta attaggggatttgggaggag aactttcctg gtgacgcttt gcttttcttc 60 tgctcttggt gagaaagtgcctccttcttc ccaggatcag gacctctgcc atccagcgcc 120 acaaagagac attctgcacacacactcaca cacacacaca cacacacact ctcacactcg 180 cccagagaca aacttaaggtgaggagaaag agcgctacct tcacttgatc tccagcttcc 240 aacttaagca gaacttgagagcatccgaac tcctggattt caggacaagt gaagaagatt 300 ctttgggcta taaag atg aagagt cta ctt ctt ctg gtg ctg att tca atc 351 Met Lys Ser Leu Leu Leu LeuVal Leu Ile Ser Ile 1 5 10 tgc tgg gct gat cat ctt tca gac aac tat actctg gat cat gac aga 399 Cys Trp Ala Asp His Leu Ser Asp Asn Tyr Thr LeuAsp His Asp Arg 15 20 25 gct att cac atc caa gca gaa aat ggc ccc cat ctactt gtg gaa gca 447 Ala Ile His Ile Gln Ala Glu Asn Gly Pro His Leu LeuVal Glu Ala 30 35 40 gag caa gcc aag gtg ttt tca cac aga ggt ggc aat gttaca ctg cca 495 Glu Gln Ala Lys Val Phe Ser His Arg Gly Gly Asn Val ThrLeu Pro 45 50 55 60 tgt aaa ttt tat cga gac cct aca gca ttt ggc tca ggaatc cat aaa 543 Cys Lys Phe Tyr Arg Asp Pro Thr Ala Phe Gly Ser Gly IleHis Lys 65 70 75 atc cga att aag tgg acc aag cta act tcg gat tac ctc aaggaa gtg 591 Ile Arg Ile Lys Trp Thr Lys Leu Thr Ser Asp Tyr Leu Lys GluVal 80 85 90 gat gtt ttt gtt tcc atg gga tac cac aaa aaa acc tat gga ggctac 639 Asp Val Phe Val Ser Met Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr95 100 105 cag ggt aga gtg ttt ctg aag gga ggc agt gat agt gat gct tctctg 687 Gln Gly Arg Val Phe Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser Leu110 115 120 gtc atc aca gac ctc act ctg gaa gat tat ggg aga tat aag tgtgag 735 Val Ile Thr Asp Leu Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu125 130 135 140 gtg att gaa gga tta gaa gat gat act gtt gtg gta gca ctggac tta 783 Val Ile Glu Gly Leu Glu Asp Asp Thr Val Val Val Ala Leu AspLeu 145 150 155 caa ggt gtg gta ttc cct tac ttt cca cga ctg ggg cgc tacaat ctc 831 Gln Gly Val Val Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr AsnLeu 160 165 170 aat ttt cac gag gcg cag cag gcg tgt ctg gac cag gat gctgtg atc 879 Asn Phe His Glu Ala Gln Gln Ala Cys Leu Asp Gln Asp Ala ValIle 175 180 185 gcc tcc ttc gac cag ctg tac gac gcc tgg cgg ggc ggg ctggac tgg 927 Ala Ser Phe Asp Gln Leu Tyr Asp Ala Trp Arg Gly Gly Leu AspTrp 190 195 200 tgc aat gcc ggc tgg ctc agt gat ggc tct gtg caa tat cccatc aca 975 Cys Asn Ala Gly Trp Leu Ser Asp Gly Ser Val Gln Tyr Pro IleThr 205 210 215 220 aag ccc aga gag ccc tgt ggg ggc cag aac aca gtg cccgga gtc agg 1023 Lys Pro Arg Glu Pro Cys Gly Gly Gln Asn Thr Val Pro GlyVal Arg 225 230 235 aac tac gga ttt tgg gat aaa gat aaa agc aga tat gatgtt ttc tgt 1071 Asn Tyr Gly Phe Trp Asp Lys Asp Lys Ser Arg Tyr Asp ValPhe Cys 240 245 250 ttt aca tcc aat ttc aat ggc cgt ttt tac tat ctg atccac ccc acc 1119 Phe Thr Ser Asn Phe Asn Gly Arg Phe Tyr Tyr Leu Ile HisPro Thr 255 260 265 aaa ctg acc tat gat gaa gcg gtg caa gct tgt ctc aatgat ggt gct 1167 Lys Leu Thr Tyr Asp Glu Ala Val Gln Ala Cys Leu Asn AspGly Ala 270 275 280 cag att gca aaa gtg ggc cag ata ttt gct gcc tgg aaaatt ctc gga 1215 Gln Ile Ala Lys Val Gly Gln Ile Phe Ala Ala Trp Lys IleLeu Gly 285 290 295 300 tat gac cgc tgt gat gcg ggc tgg ttg gcg gat ggcagc gtc cgc tac 1263 Tyr Asp Arg Cys Asp Ala Gly Trp Leu Ala Asp Gly SerVal Arg Tyr 305 310 315 ccc atc tct agg cca aga agg cgc tgc agt cct actgag gct gca gtg 1311 Pro Ile Ser Arg Pro Arg Arg Arg Cys Ser Pro Thr GluAla Ala Val 320 325 330 cgc ttc gtg ggt ttc cca gat aaa aag cat aag ctgtat ggt gtc tac 1359 Arg Phe Val Gly Phe Pro Asp Lys Lys His Lys Leu TyrGly Val Tyr 335 340 345 tgc ttc aga gca tac aac tga atgtgcccttagagcgcatc agttttaaag 1410 Cys Phe Arg Ala Tyr Asn * 350 tcattaagaacatgtgaaag gtgttttttt tttccaatat gaactcatgc aagttaccaa 1470 aactgtgataaccctttttt acttactgta aagagtcatt ttcataagat caattcattg 1530 atttgttttttgtaaagcta tcattcaata tatattataa attaatataa atttaaggga 1590 agctctatgtaaggagactt agagccaaac tgtttaagct gtatcatccc aacaaagtat 1650 cctttcatgaacggggcatg caatagctta agaattgcta ggattaaatt aaggaaagta 1710 aagctactcagagcaacagg ttccacaagc acaaacttta cacatttgta caattttgaa 1770 atgcactacaataaacaaat tagagcaaca catttgaaat acaggcttct ttacataaac 1830 tgagaggttatacaaaactc agtttcacaa gggaacaatc tatacctttc taaaagttaa 1890 tatttcaagtctctaatagg cagaatattt tactctttaa aatcctgcct ttctgaccaa 1950 aaaaaaa 195711 354 PRT Homo sapiens 11 Met Lys Ser Leu Leu Leu Leu Val Leu Ile SerIle Cys Trp Ala Asp 1 5 10 15 His Leu Ser Asp Asn Tyr Thr Leu Asp HisAsp Arg Ala Ile His Ile 20 25 30 Gln Ala Glu Asn Gly Pro His Leu Leu ValGlu Ala Glu Gln Ala Lys 35 40 45 Val Phe Ser His Arg Gly Gly Asn Val ThrLeu Pro Cys Lys Phe Tyr 50 55 60 Arg Asp Pro Thr Ala Phe Gly Ser Gly IleHis Lys Ile Arg Ile Lys 65 70 75 80 Trp Thr Lys Leu Thr Ser Asp Tyr LeuLys Glu Val Asp Val Phe Val 85 90 95 Ser Met Gly Tyr His Lys Lys Thr TyrGly Gly Tyr Gln Gly Arg Val 100 105 110 Phe Leu Lys Gly Gly Ser Asp SerAsp Ala Ser Leu Val Ile Thr Asp 115 120 125 Leu Thr Leu Glu Asp Tyr GlyArg Tyr Lys Cys Glu Val Ile Glu Gly 130 135 140 Leu Glu Asp Asp Thr ValVal Val Ala Leu Asp Leu Gln Gly Val Val 145 150 155 160 Phe Pro Tyr PhePro Arg Leu Gly Arg Tyr Asn Leu Asn Phe His Glu 165 170 175 Ala Gln GlnAla Cys Leu Asp Gln Asp Ala Val Ile Ala Ser Phe Asp 180 185 190 Gln LeuTyr Asp Ala Trp Arg Gly Gly Leu Asp Trp Cys Asn Ala Gly 195 200 205 TrpLeu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr Lys Pro Arg Glu 210 215 220Pro Cys Gly Gly Gln Asn Thr Val Pro Gly Val Arg Asn Tyr Gly Phe 225 230235 240 Trp Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys Phe Thr Ser Asn245 250 255 Phe Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr Lys Leu ThrTyr 260 265 270 Asp Glu Ala Val Gln Ala Cys Leu Asn Asp Gly Ala Gln IleAla Lys 275 280 285 Val Gly Gln Ile Phe Ala Ala Trp Lys Ile Leu Gly TyrAsp Arg Cys 290 295 300 Asp Ala Gly Trp Leu Ala Asp Gly Ser Val Arg TyrPro Ile Ser Arg 305 310 315 320 Pro Arg Arg Arg Cys Ser Pro Thr Glu AlaAla Val Arg Phe Val Gly 325 330 335 Phe Pro Asp Lys Lys His Lys Leu TyrGly Val Tyr Cys Phe Arg Ala 340 345 350 Tyr Asn 12 1957 DNA Homo sapiensCDS (316)...(1380) 12 ttaggctgta attaggggat ttgggaggag aactttcctggtgacgcttt gcttttcttc 60 tgctcttggt gagaaagtgc ctccttcttc ccaggatcaggacctctgcc atccagcgcc 120 acaaagagac attctgcaca cacactcaca cacacacacacacacacact ctcacactcg 180 cccagagaca aacttaaggt gaggagaaag agcgctacgttcacttgatc tccagcttcc 240 aacttaagca gaacttgaga gcatccgaac tcctggatttcaggacaagt gaagaagatt 300 ctttgggcta taaag atg aag agt cta ctt ctt ctggtg ctg att tca atc 351 Met Lys Ser Leu Leu Leu Leu Val Leu Ile Ser Ile1 5 10 tgc tgg gct gat cat ctt tca gac aac tat act ctg gat cat gac aga399 Cys Trp Ala Asp His Leu Ser Asp Asn Tyr Thr Leu Asp His Asp Arg 1520 25 gct att cac atc caa gca gaa aat ggc ccc cat cta ctt gtg gaa gca447 Ala Ile His Ile Gln Ala Glu Asn Gly Pro His Leu Leu Val Glu Ala 3035 40 gag caa gcc aag gtg ttt tca cac aga ggt ggc aat gtt aca ctg cca495 Glu Gln Ala Lys Val Phe Ser His Arg Gly Gly Asn Val Thr Leu Pro 4550 55 60 tgt aaa ttt tat cga gac cct aca gca ttt ggc tca gga atc cat aaa543 Cys Lys Phe Tyr Arg Asp Pro Thr Ala Phe Gly Ser Gly Ile His Lys 6570 75 atc cga att aag tgg acc aag cta act tcg gat tac ctc aag gaa gtg591 Ile Arg Ile Lys Trp Thr Lys Leu Thr Ser Asp Tyr Leu Lys Glu Val 8085 90 gat gtt ttt gtt tcc atg gga tac cac aaa aaa acc tat gga ggc tac639 Asp Val Phe Val Ser Met Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr 95100 105 cag ggt aga gtg ttt ctg aag gga ggc agt gat agt gat gct tct ctg687 Gln Gly Arg Val Phe Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser Leu 110115 120 gtc atc aca gac ctc act ctg gaa gat tat ggg aga tat aag tgt gag735 Val Ile Thr Asp Leu Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu 125130 135 140 gtg att gaa gga tta gaa gat gat act gtt gtg gta gca ctg gactta 783 Val Ile Glu Gly Leu Glu Asp Asp Thr Val Val Val Ala Leu Asp Leu145 150 155 caa ggt gtg gta ttc cct tac ttt cca cga ctg ggg cgc tac aatctc 831 Gln Gly Val Val Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu160 165 170 aat ttt cac gag gcg cag cag gcg tgt ctg gac cag gat gct gtgatc 879 Asn Phe His Glu Ala Gln Gln Ala Cys Leu Asp Gln Asp Ala Val Ile175 180 185 gcc tcc ttc gac cag ctg tac gac gcc tgg cgg ggc ggg ctg gactgg 927 Ala Ser Phe Asp Gln Leu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp190 195 200 tgc aat gcc ggc tgg ctc agt gat ggc tct gtg caa tat ccc atcaca 975 Cys Asn Ala Gly Trp Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr205 210 215 220 aag ccc aga gag ccc tgt ggg ggg cag aac aca gtg ccc ggagtc agg 1023 Lys Pro Arg Glu Pro Cys Gly Gly Gln Asn Thr Val Pro Gly ValArg 225 230 235 aac tac gga ttt tgg gat aaa gat aaa agc aga tat gat gttttc tgt 1071 Asn Tyr Gly Phe Trp Asp Lys Asp Lys Ser Arg Tyr Asp Val PheCys 240 245 250 ttt aca tcc aat ttc aat ggc cgt ttt tac tat ctg atc cacccc acc 1119 Phe Thr Ser Asn Phe Asn Gly Arg Phe Tyr Tyr Leu Ile His ProThr 255 260 265 aaa ctg acc tat gat gaa gcg gtg caa gct tgt ctc aat gatggt gct 1167 Lys Leu Thr Tyr Asp Glu Ala Val Gln Ala Cys Leu Asn Asp GlyAla 270 275 280 cag att gca aaa gtg ggc cag ata ttt gct gcc tgg aaa attctc gga 1215 Gln Ile Ala Lys Val Gly Gln Ile Phe Ala Ala Trp Lys Ile LeuGly 285 290 295 300 tat gac cgc tgt gat gcg ggc tgg ttg gcg gat ggc agcgtc cgc tac 1263 Tyr Asp Arg Cys Asp Ala Gly Trp Leu Ala Asp Gly Ser ValArg Tyr 305 310 315 ccc atc tct agg cca aga agg cgc tgc agt cct act gaggct gca gtg 1311 Pro Ile Ser Arg Pro Arg Arg Arg Cys Ser Pro Thr Glu AlaAla Val 320 325 330 cgc ttc gtg ggt ttc cca gat aaa aag cat aag ctg tatggt gtc tac 1359 Arg Phe Val Gly Phe Pro Asp Lys Lys His Lys Leu Tyr GlyVal Tyr 335 340 345 tgc ttc aga gca tac aac tga atgtgccctt agagcgcatcagttttaaag 1410 Cys Phe Arg Ala Tyr Asn * 350 tcattaagaa catgtgaaaggtgttttttt tttccaatat gaactcatgc aagttaccaa 1470 aactgtgata acccttttttacttactgta aagagtcatt ttcataagat caattcattg 1530 atttgttttt tgtaaagctatcattcaata tatattataa attaatataa atttaaggga 1590 agctctatgt aaggagacttagagccaaac tgtttaagct gtatcatccc aacaaagtat 1650 cctttcatga acggggcatgcaatagctta agaattgcta ggattaaatt aaggaaagta 1710 aagctactca gagcaacaggttccacaagc acaaacttta cacatttgta caattttgaa 1770 atgcactaca ataaacaaattagagcaaca catttgaaat acaggcttct ttacataaac 1830 tgagaggtta tacaaaactcagtttcacaa gggaacaatc tatacctttc taaaagttaa 1890 tatttcaagt ctctaataggcagaatattt tactctttaa aatcctgcct ttctgaccaa 1950 aaaaaaa 1957 13 354 PRTHomo sapiens 13 Met Lys Ser Leu Leu Leu Leu Val Leu Ile Ser Ile Cys TrpAla Asp 1 5 10 15 His Leu Ser Asp Asn Tyr Thr Leu Asp His Asp Arg AlaIle His Ile 20 25 30 Gln Ala Glu Asn Gly Pro His Leu Leu Val Glu Ala GluGln Ala Lys 35 40 45 Val Phe Ser His Arg Gly Gly Asn Val Thr Leu Pro CysLys Phe Tyr 50 55 60 Arg Asp Pro Thr Ala Phe Gly Ser Gly Ile His Lys IleArg Ile Lys 65 70 75 80 Trp Thr Lys Leu Thr Ser Asp Tyr Leu Lys Glu ValAsp Val Phe Val 85 90 95 Ser Met Gly Tyr His Lys Lys Thr Tyr Gly Gly TyrGln Gly Arg Val 100 105 110 Phe Leu Lys Gly Gly Ser Asp Ser Asp Ala SerLeu Val Ile Thr Asp 115 120 125 Leu Thr Leu Glu Asp Tyr Gly Arg Tyr LysCys Glu Val Ile Glu Gly 130 135 140 Leu Glu Asp Asp Thr Val Val Val AlaLeu Asp Leu Gln Gly Val Val 145 150 155 160 Phe Pro Tyr Phe Pro Arg LeuGly Arg Tyr Asn Leu Asn Phe His Glu 165 170 175 Ala Gln Gln Ala Cys LeuAsp Gln Asp Ala Val Ile Ala Ser Phe Asp 180 185 190 Gln Leu Tyr Asp AlaTrp Arg Gly Gly Leu Asp Trp Cys Asn Ala Gly 195 200 205 Trp Leu Ser AspGly Ser Val Gln Tyr Pro Ile Thr Lys Pro Arg Glu 210 215 220 Pro Cys GlyGly Gln Asn Thr Val Pro Gly Val Arg Asn Tyr Gly Phe 225 230 235 240 TrpAsp Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys Phe Thr Ser Asn 245 250 255Phe Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr Lys Leu Thr Tyr 260 265270 Asp Glu Ala Val Gln Ala Cys Leu Asn Asp Gly Ala Gln Ile Ala Lys 275280 285 Val Gly Gln Ile Phe Ala Ala Trp Lys Ile Leu Gly Tyr Asp Arg Cys290 295 300 Asp Ala Gly Trp Leu Ala Asp Gly Ser Val Arg Tyr Pro Ile SerArg 305 310 315 320 Pro Arg Arg Arg Cys Ser Pro Thr Glu Ala Ala Val ArgPhe Val Gly 325 330 335 Phe Pro Asp Lys Lys His Lys Leu Tyr Gly Val TyrCys Phe Arg Ala 340 345 350 Tyr Asn 14 1957 DNA Homo sapiens CDS(316)...(1380) 14 ttaggctgta attaggggat ttgggaggag aactttcctg gtgacgctttgcttttcttc 60 tgctcttggt gagaaagtgc ctccttcttc ccaggatcag gacctctgccatccagcgcc 120 acaaagagac attctgcaca cacactcaca cacacacaca cacacacactctcacactcg 180 cccagagaca aacttaaggt gaggagaaag agcgctacgt tcacttgatctccagcttcc 240 aacttaagca gaacttgaga gcatccgaac tcctggattt caggacaagtgaagaagatt 300 ctttgggcta taaag atg aag agt cta ctt ctt ctg gtg ctg atttca atc 351 Met Lys Ser Leu Leu Leu Leu Val Leu Ile Ser Ile 1 5 10 tgctgg gct gat cat ctt tca gac aac tat act ctg gat cat gac aga 399 Cys TrpAla Asp His Leu Ser Asp Asn Tyr Thr Leu Asp His Asp Arg 15 20 25 gct attcac atc caa gca gaa aat ggc ccc cat cta ctt gtg gaa gca 447 Ala Ile HisIle Gln Ala Glu Asn Gly Pro His Leu Leu Val Glu Ala 30 35 40 gag caa gccaag gtg ttt tca cac aga ggt ggc aat gtt aca ctg cca 495 Glu Gln Ala LysVal Phe Ser His Arg Gly Gly Asn Val Thr Leu Pro 45 50 55 60 tgt aaa ttttat cga gac cct aca gca ttt ggc tca gga atc cat aaa 543 Cys Lys Phe TyrArg Asp Pro Thr Ala Phe Gly Ser Gly Ile His Lys 65 70 75 atc cga att aagtgg acc aag cta act tcg gat tac ctc aag gaa gtg 591 Ile Arg Ile Lys TrpThr Lys Leu Thr Ser Asp Tyr Leu Lys Glu Val 80 85 90 gat gtt ttt gtt tccatg gga tac cac aaa aaa acc tat gga ggc tac 639 Asp Val Phe Val Ser MetGly Tyr His Lys Lys Thr Tyr Gly Gly Tyr 95 100 105 cag ggt aga gtg tttctg aag gga ggc agt gat agt gat gct tct ctg 687 Gln Gly Arg Val Phe LeuLys Gly Gly Ser Asp Ser Asp Ala Ser Leu 110 115 120 gtc atc aca gac ctcact ctg gaa gat tat ggg aga tat aag tgt gag 735 Val Ile Thr Asp Leu ThrLeu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu 125 130 135 140 gtg att gaa ggatta gaa gat gat act gtt gtg gta gca ctg gac tta 783 Val Ile Glu Gly LeuGlu Asp Asp Thr Val Val Val Ala Leu Asp Leu 145 150 155 caa ggt gtg gtattc cct tac ttt cca cga ctg ggg cgc tac aat ctc 831 Gln Gly Val Val PhePro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu 160 165 170 aat ttt cac gaggcg cag cag gcg tgt ctg gac cag gat gct gtg atc 879 Asn Phe His Glu AlaGln Gln Ala Cys Leu Asp Gln Asp Ala Val Ile 175 180 185 gcc tcc ttc gaccag ctg tac gac gcc tgg cgg ggc ggg ctg gac tgg 927 Ala Ser Phe Asp GlnLeu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp 190 195 200 tgc aat gcc ggctgg ctc agt gat ggc tct gtg caa tat ccc atc aca 975 Cys Asn Ala Gly TrpLeu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr 205 210 215 220 aag ccc agagag ccc tgt ggg ggc cag aac aca gtg ccc gga gtc agg 1023 Lys Pro Arg GluPro Cys Gly Gly Gln Asn Thr Val Pro Gly Val Arg 225 230 235 aac tac ggattt tgg gat aaa gat aaa agc aga tat gat gtt ttc tgt 1071 Asn Tyr Gly PheTrp Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys 240 245 250 ttt aca tccaat ttc aat ggc cgt ttt tac tat ctg atc cac ccc acc 1119 Phe Thr Ser AsnPhe Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr 255 260 265 aaa ctg acctat gat gaa gcg gtg caa gct tgt ctc aat gat ggt gct 1167 Lys Leu Thr TyrAsp Glu Ala Val Gln Ala Cys Leu Asn Asp Gly Ala 270 275 280 cag att gcaaaa gtg ggc cag ata ttt gct gcc tgg aaa att ctc gga 1215 Gln Ile Ala LysVal Gly Gln Ile Phe Ala Ala Trp Lys Ile Leu Gly 285 290 295 300 tat gaccgc tgt gat gcg ggc tgg ttg gcg gat ggc agc gtc cgc tac 1263 Tyr Asp ArgCys Asp Ala Gly Trp Leu Ala Asp Gly Ser Val Arg Tyr 305 310 315 ccc atctct agg cca aga agg cgc tgc agt cct act gag gct gca gtg 1311 Pro Ile SerArg Pro Arg Arg Arg Cys Ser Pro Thr Glu Ala Ala Val 320 325 330 cgc ttcgtg ggt ttt cca gat aaa aag cat aag ctg tat ggt gtc tac 1359 Arg Phe ValGly Phe Pro Asp Lys Lys His Lys Leu Tyr Gly Val Tyr 335 340 345 tgc ttcaga gca tac aac tga atgtgccctt agagcgcatc agttttaaag 1410 Cys Phe ArgAla Tyr Asn * 350 tcattaagaa catgtgaaag gtgttttttt tttccaatat gaactcatgcaagttaccaa 1470 aactgtgata accctttttt acttactgta aagagtcatt ttcataagatcaattcattg 1530 atttgttttt tgtaaagcta tcattcaata tatattataa attaatataaatttaaggga 1590 agctctatgt aaggagactt agagccaaac tgtttaagct gtatcatcccaacaaagtat 1650 cctttcatga acggggcatg caatagctta agaattgcta ggattaaattaaggaaagta 1710 aagctactca gagcaacagg ttccacaagc acaaacttta cacatttgtacaattttgaa 1770 atgcactaca ataaacaaat tagagcaaca catttgaaat acaggcttctttacataaac 1830 tgagaggtta tacaaaactc agtttcacaa gggaacaatc tatacctttctaaaagttaa 1890 tatttcaagt ctctaatagg cagaatattt tactctttaa aatcctgcctttctgaccaa 1950 aaaaaaa 1957 15 354 PRT Homo sapiens 15 Met Lys Ser LeuLeu Leu Leu Val Leu Ile Ser Ile Cys Trp Ala Asp 1 5 10 15 His Leu SerAsp Asn Tyr Thr Leu Asp His Asp Arg Ala Ile His Ile 20 25 30 Gln Ala GluAsn Gly Pro His Leu Leu Val Glu Ala Glu Gln Ala Lys 35 40 45 Val Phe SerHis Arg Gly Gly Asn Val Thr Leu Pro Cys Lys Phe Tyr 50 55 60 Arg Asp ProThr Ala Phe Gly Ser Gly Ile His Lys Ile Arg Ile Lys 65 70 75 80 Trp ThrLys Leu Thr Ser Asp Tyr Leu Lys Glu Val Asp Val Phe Val 85 90 95 Ser MetGly Tyr His Lys Lys Thr Tyr Gly Gly Tyr Gln Gly Arg Val 100 105 110 PheLeu Lys Gly Gly Ser Asp Ser Asp Ala Ser Leu Val Ile Thr Asp 115 120 125Leu Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu Val Ile Glu Gly 130 135140 Leu Glu Asp Asp Thr Val Val Val Ala Leu Asp Leu Gln Gly Val Val 145150 155 160 Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu Asn Phe HisGlu 165 170 175 Ala Gln Gln Ala Cys Leu Asp Gln Asp Ala Val Ile Ala SerPhe Asp 180 185 190 Gln Leu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp CysAsn Ala Gly 195 200 205 Trp Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile ThrLys Pro Arg Glu 210 215 220 Pro Cys Gly Gly Gln Asn Thr Val Pro Gly ValArg Asn Tyr Gly Phe 225 230 235 240 Trp Asp Lys Asp Lys Ser Arg Tyr AspVal Phe Cys Phe Thr Ser Asn 245 250 255 Phe Asn Gly Arg Phe Tyr Tyr LeuIle His Pro Thr Lys Leu Thr Tyr 260 265 270 Asp Glu Ala Val Gln Ala CysLeu Asn Asp Gly Ala Gln Ile Ala Lys 275 280 285 Val Gly Gln Ile Phe AlaAla Trp Lys Ile Leu Gly Tyr Asp Arg Cys 290 295 300 Asp Ala Gly Trp LeuAla Asp Gly Ser Val Arg Tyr Pro Ile Ser Arg 305 310 315 320 Pro Arg ArgArg Cys Ser Pro Thr Glu Ala Ala Val Arg Phe Val Gly 325 330 335 Phe ProAsp Lys Lys His Lys Leu Tyr Gly Val Tyr Cys Phe Arg Ala 340 345 350 TyrAsn 16 1957 DNA Homo sapiens CDS (316)...(1380) 16 ttaggctgta attaggggatttgggaggag aactttcctg gtgacgcttt gcttttcttc 60 tgctcttggt gagaaagtgcctccttcttc ccaggatcag gacctctgcc atccagcgcc 120 acaaagagac attctgcacacacactcaca cacacacaca cacacacact ctcacactcg 180 cccagagaca aacttaaggtgaggagaaag agcgctacgt tcacttgatc tccagcttcc 240 aacttaagca gaacttgagagcatccgaac tcctggattt caggacaagt gaagaagatt 300 ctttgggcta taaag atg aagagt cta ctt ctt ctg gtg ctg att tca atc 351 Met Lys Ser Leu Leu Leu LeuVal Leu Ile Ser Ile 1 5 10 tgc tgg gct gat cat ctt tca gac aac tat actctg gat cat gac aga 399 Cys Trp Ala Asp His Leu Ser Asp Asn Tyr Thr LeuAsp His Asp Arg 15 20 25 gct att cac atc caa gca gaa aat ggc ccc cat ctactt gtg gaa gca 447 Ala Ile His Ile Gln Ala Glu Asn Gly Pro His Leu LeuVal Glu Ala 30 35 40 gag caa gcc aag gtg ttt tca cac aga ggt ggc aat gttaca ctg cca 495 Glu Gln Ala Lys Val Phe Ser His Arg Gly Gly Asn Val ThrLeu Pro 45 50 55 60 tgt aaa ttt tat cga gac cct aca gca ttt ggc tca ggaatc cat aaa 543 Cys Lys Phe Tyr Arg Asp Pro Thr Ala Phe Gly Ser Gly IleHis Lys 65 70 75 atc cga att aag tgg acc aag cta act tcg gat tac ctc aaggaa gtg 591 Ile Arg Ile Lys Trp Thr Lys Leu Thr Ser Asp Tyr Leu Lys GluVal 80 85 90 gat gtt ttt gtt tcc atg gga tac cac aaa aaa acc tat gga ggctac 639 Asp Val Phe Val Ser Met Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr95 100 105 cag ggt aga gtg ttt ctg aag gga ggc agt gat agt gat gct tctctg 687 Gln Gly Arg Val Phe Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser Leu110 115 120 gtc atc aca gac ctc act ctg gaa gat tat ggg aga tat aag tgtgag 735 Val Ile Thr Asp Leu Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu125 130 135 140 gtg att gaa gga tta gaa gat gat act gtt gtg gta gca ctggac tta 783 Val Ile Glu Gly Leu Glu Asp Asp Thr Val Val Val Ala Leu AspLeu 145 150 155 caa ggt gtg gta ttc cct tac ttt cca cga ctg ggg cgc tacaat ctc 831 Gln Gly Val Val Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr AsnLeu 160 165 170 aat ttt cac gag gcg cag cag gcg tgt ctg gac cag gat gctgtg atc 879 Asn Phe His Glu Ala Gln Gln Ala Cys Leu Asp Gln Asp Ala ValIle 175 180 185 gcc tcc ttc gac cag ctg tac gac gcc tgg cgg ggc ggg ctggac tgg 927 Ala Ser Phe Asp Gln Leu Tyr Asp Ala Trp Arg Gly Gly Leu AspTrp 190 195 200 tgc aat gcc ggc tgg ctc agt gat ggc tct gtg caa tat cccatc aca 975 Cys Asn Ala Gly Trp Leu Ser Asp Gly Ser Val Gln Tyr Pro IleThr 205 210 215 220 aag ccc aga gag ccc tgt ggg ggc cag aac aca gtg cccgga gtc agg 1023 Lys Pro Arg Glu Pro Cys Gly Gly Gln Asn Thr Val Pro GlyVal Arg 225 230 235 aac tac gga ttt tgg gat aaa gat aaa agc aga tat gatgtt ttc tgt 1071 Asn Tyr Gly Phe Trp Asp Lys Asp Lys Ser Arg Tyr Asp ValPhe Cys 240 245 250 ttt aca tcc aat ttc aat ggc cgt ttt tac tat ctg atccac ccc acc 1119 Phe Thr Ser Asn Phe Asn Gly Arg Phe Tyr Tyr Leu Ile HisPro Thr 255 260 265 aaa ctg acc tat gat gaa gcg gtg caa gct tgt ctc aatgat ggt gct 1167 Lys Leu Thr Tyr Asp Glu Ala Val Gln Ala Cys Leu Asn AspGly Ala 270 275 280 cag att gca aaa gtg ggc cag ata ttt gct gcc tgg aaaatt ctc gga 1215 Gln Ile Ala Lys Val Gly Gln Ile Phe Ala Ala Trp Lys IleLeu Gly 285 290 295 300 tat gac cgc tgt gat gcg ggc tgg ttg gcg gat ggcagc gtc cgc tac 1263 Tyr Asp Arg Cys Asp Ala Gly Trp Leu Ala Asp Gly SerVal Arg Tyr 305 310 315 ccc atc tct agg cca aga agg cgc tgc agt cct actgag gct gca gtg 1311 Pro Ile Ser Arg Pro Arg Arg Arg Cys Ser Pro Thr GluAla Ala Val 320 325 330 cgc ttc gtg ggt ttc cca gat aaa aag cat aag ctgtat ggt gtc tac 1359 Arg Phe Val Gly Phe Pro Asp Lys Lys His Lys Leu TyrGly Val Tyr 335 340 345 tgc ttc aga gca tac aac tga atgtgcccttagagcgcacc agttttaaag 1410 Cys Phe Arg Ala Tyr Asn * 350 tcattaagaacatgtgaaag gtgttttttt tttccaatat gaactcatgc aagttaccaa 1470 aactgtgataaccctttttt acttactgta aagagtcatt ttcataagat caattcattg 1530 atttgttttttgtaaagcta tcattcaata tatattataa attaatataa atttaaggga 1590 agctctatgtaaggagactt agagccaaac tgtttaagct gtatcatccc aacaaagtat 1650 cctttcatgaacggggcatg caatagctta agaattgcta ggattaaatt aaggaaagta 1710 aagctactcagagcaacagg ttccacaagc acaaacttta cacatttgta caattttgaa 1770 atgcactacaataaacaaat tagagcaaca catttgaaat acaggcttct ttacataaac 1830 tgagaggttatacaaaactc agtttcacaa gggaacaatc tatacctttc taaaagttaa 1890 tatttcaagtctctaatagg cagaatattt tactctttaa aatcctgcct ttctgaccaa 1950 aaaaaaa 195717 354 PRT Homo sapiens 17 Met Lys Ser Leu Leu Leu Leu Val Leu Ile SerIle Cys Trp Ala Asp 1 5 10 15 His Leu Ser Asp Asn Tyr Thr Leu Asp HisAsp Arg Ala Ile His Ile 20 25 30 Gln Ala Glu Asn Gly Pro His Leu Leu ValGlu Ala Glu Gln Ala Lys 35 40 45 Val Phe Ser His Arg Gly Gly Asn Val ThrLeu Pro Cys Lys Phe Tyr 50 55 60 Arg Asp Pro Thr Ala Phe Gly Ser Gly IleHis Lys Ile Arg Ile Lys 65 70 75 80 Trp Thr Lys Leu Thr Ser Asp Tyr LeuLys Glu Val Asp Val Phe Val 85 90 95 Ser Met Gly Tyr His Lys Lys Thr TyrGly Gly Tyr Gln Gly Arg Val 100 105 110 Phe Leu Lys Gly Gly Ser Asp SerAsp Ala Ser Leu Val Ile Thr Asp 115 120 125 Leu Thr Leu Glu Asp Tyr GlyArg Tyr Lys Cys Glu Val Ile Glu Gly 130 135 140 Leu Glu Asp Asp Thr ValVal Val Ala Leu Asp Leu Gln Gly Val Val 145 150 155 160 Phe Pro Tyr PhePro Arg Leu Gly Arg Tyr Asn Leu Asn Phe His Glu 165 170 175 Ala Gln GlnAla Cys Leu Asp Gln Asp Ala Val Ile Ala Ser Phe Asp 180 185 190 Gln LeuTyr Asp Ala Trp Arg Gly Gly Leu Asp Trp Cys Asn Ala Gly 195 200 205 TrpLeu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr Lys Pro Arg Glu 210 215 220Pro Cys Gly Gly Gln Asn Thr Val Pro Gly Val Arg Asn Tyr Gly Phe 225 230235 240 Trp Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys Phe Thr Ser Asn245 250 255 Phe Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr Lys Leu ThrTyr 260 265 270 Asp Glu Ala Val Gln Ala Cys Leu Asn Asp Gly Ala Gln IleAla Lys 275 280 285 Val Gly Gln Ile Phe Ala Ala Trp Lys Ile Leu Gly TyrAsp Arg Cys 290 295 300 Asp Ala Gly Trp Leu Ala Asp Gly Ser Val Arg TyrPro Ile Ser Arg 305 310 315 320 Pro Arg Arg Arg Cys Ser Pro Thr Glu AlaAla Val Arg Phe Val Gly 325 330 335 Phe Pro Asp Lys Lys His Lys Leu TyrGly Val Tyr Cys Phe Arg Ala 340 345 350 Tyr Asn 18 1957 DNA Homo sapiensCDS (316)...(1380) 18 ttaggctgta attaggggat ttgggaggag aactttcctggtgacgcttt gcttttcttc 60 tgctcttggt gagaaagtgc ctccttcttc ccaggatcaggacctctgcc atccagcgcc 120 acaaagagac attctgcaca cacactcaca cacacacacacacacacact ctcacactcg 180 cccagagaca aacttaaggt gaggagaaag agcgctacgttcacttgatc tccagcttcc 240 aacttaagca gaacttgaga gcatccgaac tcctggatttcaggacaagt gaagaagatt 300 ctttgggcta taaag atg aag agt cta ctt ctt ctggtg ctg att tca atc 351 Met Lys Ser Leu Leu Leu Leu Val Leu Ile Ser Ile1 5 10 tgc tgg gct gat cat ctt tca gac aac tat act ctg gat cat gac aga399 Cys Trp Ala Asp His Leu Ser Asp Asn Tyr Thr Leu Asp His Asp Arg 1520 25 gct att cac atc caa gca gaa aat ggc ccc cat cta ctt gtg gaa gca447 Ala Ile His Ile Gln Ala Glu Asn Gly Pro His Leu Leu Val Glu Ala 3035 40 gag caa gcc aag gtg ttt tca cac aga ggt ggc aat gtt aca ctg cca495 Glu Gln Ala Lys Val Phe Ser His Arg Gly Gly Asn Val Thr Leu Pro 4550 55 60 tgt aaa ttt tat cga gac cct aca gca ttt ggc tca gga atc cat aaa543 Cys Lys Phe Tyr Arg Asp Pro Thr Ala Phe Gly Ser Gly Ile His Lys 6570 75 atc cga att aag tgg acc aag cta act tcg gat tac ctc aag gaa gtg591 Ile Arg Ile Lys Trp Thr Lys Leu Thr Ser Asp Tyr Leu Lys Glu Val 8085 90 gat gtt ttt gtt tcc atg gga tac cac aaa aaa acc tat gga ggc tac639 Asp Val Phe Val Ser Met Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr 95100 105 cag ggt aga gtg ttt ctg aag gga ggc agt gat agt gat gct tct ctg687 Gln Gly Arg Val Phe Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser Leu 110115 120 gtc atc aca gac ctc act ctg gaa gat tat ggg aga tat aag tgt gag735 Val Ile Thr Asp Leu Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu 125130 135 140 gtg att gaa gga tta gaa gat gat act gtt gtg gta gca ctg gactta 783 Val Ile Glu Gly Leu Glu Asp Asp Thr Val Val Val Ala Leu Asp Leu145 150 155 caa ggt gtg gta ttc cct tac ttt cca cga ctg ggg cgc tac aatctc 831 Gln Gly Val Val Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu160 165 170 aat ttt cac gag gcg cag cag gcg tgt ctg gac cag gat gct gtgatc 879 Asn Phe His Glu Ala Gln Gln Ala Cys Leu Asp Gln Asp Ala Val Ile175 180 185 gcc tcc ttc gac cag ctg tac gac gcc tgg cgg ggc ggg ctg gactgg 927 Ala Ser Phe Asp Gln Leu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp190 195 200 tgc aat gcc ggc tgg ctc agt gat ggc tct gtg caa tat ccc atcaca 975 Cys Asn Ala Gly Trp Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr205 210 215 220 aag ccc aga gag ccc tgt ggg ggc cag aac aca gtg ccc ggagtc agg 1023 Lys Pro Arg Glu Pro Cys Gly Gly Gln Asn Thr Val Pro Gly ValArg 225 230 235 aac tac gga ttt tgg gat aaa gat aaa agc aga tat gat gttttc tgt 1071 Asn Tyr Gly Phe Trp Asp Lys Asp Lys Ser Arg Tyr Asp Val PheCys 240 245 250 ttt aca tcc aat ttc aat ggc cgt ttt tac tat ctg atc cacccc acc 1119 Phe Thr Ser Asn Phe Asn Gly Arg Phe Tyr Tyr Leu Ile His ProThr 255 260 265 aaa ctg acc tat gat gaa gcg gtg caa gct tgt ctc aat gatggt gct 1167 Lys Leu Thr Tyr Asp Glu Ala Val Gln Ala Cys Leu Asn Asp GlyAla 270 275 280 cag att gca aaa gtg ggc cag ata ttt gct gcc tgg aaa attctc gga 1215 Gln Ile Ala Lys Val Gly Gln Ile Phe Ala Ala Trp Lys Ile LeuGly 285 290 295 300 tat gac cgc tgt gat gcg ggc tgg ttg gcg gat ggc agcgtc cgc tac 1263 Tyr Asp Arg Cys Asp Ala Gly Trp Leu Ala Asp Gly Ser ValArg Tyr 305 310 315 ccc atc tct agg cca aga agg cgc tgc agt cct act gaggct gca gtg 1311 Pro Ile Ser Arg Pro Arg Arg Arg Cys Ser Pro Thr Glu AlaAla Val 320 325 330 cgc ttc gtg ggt ttc cca gat aaa aag cat aag ctg tatggt gtc tac 1359 Arg Phe Val Gly Phe Pro Asp Lys Lys His Lys Leu Tyr GlyVal Tyr 335 340 345 tgc ttc aga gca tac aac tga atgtgccctt agagcgcattagttttaaag 1410 Cys Phe Arg Ala Tyr Asn * 350 tcattaagaa catgtgaaaggtgttttttt tttccaatat gaactcatgc aagttaccaa 1470 aactgtgata acccttttttacttactgta aagagtcatt ttcataagat caattcattg 1530 atttgttttt tgtaaagctatcattcaata tatattataa attaatataa atttaaggga 1590 agctctatgt aaggagacttagagccaaac tgtttaagct gtatcatccc aacaaagtat 1650 cctttcatga acggggcatgcaatagctta agaattgcta ggattaaatt aaggaaagta 1710 aagctactca gagcaacaggttccacaagc acaaacttta cacatttgta caattttgaa 1770 atgcactaca ataaacaaattagagcaaca catttgaaat acaggcttct ttacataaac 1830 tgagaggtta tacaaaactcagtttcacaa gggaacaatc tatacctttc taaaagttaa 1890 tatttcaagt ctctaataggcagaatattt tactctttaa aatcctgcct ttctgaccaa 1950 aaaaaaa 1957 19 354 PRTHomo sapiens 19 Met Lys Ser Leu Leu Leu Leu Val Leu Ile Ser Ile Cys TrpAla Asp 1 5 10 15 His Leu Ser Asp Asn Tyr Thr Leu Asp His Asp Arg AlaIle His Ile 20 25 30 Gln Ala Glu Asn Gly Pro His Leu Leu Val Glu Ala GluGln Ala Lys 35 40 45 Val Phe Ser His Arg Gly Gly Asn Val Thr Leu Pro CysLys Phe Tyr 50 55 60 Arg Asp Pro Thr Ala Phe Gly Ser Gly Ile His Lys IleArg Ile Lys 65 70 75 80 Trp Thr Lys Leu Thr Ser Asp Tyr Leu Lys Glu ValAsp Val Phe Val 85 90 95 Ser Met Gly Tyr His Lys Lys Thr Tyr Gly Gly TyrGln Gly Arg Val 100 105 110 Phe Leu Lys Gly Gly Ser Asp Ser Asp Ala SerLeu Val Ile Thr Asp 115 120 125 Leu Thr Leu Glu Asp Tyr Gly Arg Tyr LysCys Glu Val Ile Glu Gly 130 135 140 Leu Glu Asp Asp Thr Val Val Val AlaLeu Asp Leu Gln Gly Val Val 145 150 155 160 Phe Pro Tyr Phe Pro Arg LeuGly Arg Tyr Asn Leu Asn Phe His Glu 165 170 175 Ala Gln Gln Ala Cys LeuAsp Gln Asp Ala Val Ile Ala Ser Phe Asp 180 185 190 Gln Leu Tyr Asp AlaTrp Arg Gly Gly Leu Asp Trp Cys Asn Ala Gly 195 200 205 Trp Leu Ser AspGly Ser Val Gln Tyr Pro Ile Thr Lys Pro Arg Glu 210 215 220 Pro Cys GlyGly Gln Asn Thr Val Pro Gly Val Arg Asn Tyr Gly Phe 225 230 235 240 TrpAsp Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys Phe Thr Ser Asn 245 250 255Phe Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr Lys Leu Thr Tyr 260 265270 Asp Glu Ala Val Gln Ala Cys Leu Asn Asp Gly Ala Gln Ile Ala Lys 275280 285 Val Gly Gln Ile Phe Ala Ala Trp Lys Ile Leu Gly Tyr Asp Arg Cys290 295 300 Asp Ala Gly Trp Leu Ala Asp Gly Ser Val Arg Tyr Pro Ile SerArg 305 310 315 320 Pro Arg Arg Arg Cys Ser Pro Thr Glu Ala Ala Val ArgPhe Val Gly 325 330 335 Phe Pro Asp Lys Lys His Lys Leu Tyr Gly Val TyrCys Phe Arg Ala 340 345 350 Tyr Asn 20 1957 DNA Homo sapiens CDS(316)...(1380) 20 ttaggctgta attaggggat ttgggaggag aactttcctg gtgacgctttgcttttcttc 60 tgctcttggt gagaaagtgc ctccttcttc ccaggatcag gacctctgccatccagcgcc 120 acaaagagac attctgcaca cacactcaca cacacacaca cacacacactctcacactcg 180 cccagagaca aacttaaggt gaggagaaag agcgctacgt tcacttgatctccagcttcc 240 aacttaagca gaacttgaga gcatccgaac tcctggattt caggacaagtgaagaagatt 300 ctttgggcta taaag atg aag agt cta ctt ctt ctg gtg ctg atttca atc 351 Met Lys Ser Leu Leu Leu Leu Val Leu Ile Ser Ile 1 5 10 tgctgg gct gat cat ctt tca gac aac tat act ctg gat cat gac aga 399 Cys TrpAla Asp His Leu Ser Asp Asn Tyr Thr Leu Asp His Asp Arg 15 20 25 gct attcac atc caa gca gaa aat ggc ccc cat cta ctt gtg gaa gca 447 Ala Ile HisIle Gln Ala Glu Asn Gly Pro His Leu Leu Val Glu Ala 30 35 40 gag caa gccaag gtg ttt tca cac aga ggt ggc aat gtt aca ctg cca 495 Glu Gln Ala LysVal Phe Ser His Arg Gly Gly Asn Val Thr Leu Pro 45 50 55 60 tgt aaa ttttat cga gac cct aca gca ttt ggc tca gga atc cat aaa 543 Cys Lys Phe TyrArg Asp Pro Thr Ala Phe Gly Ser Gly Ile His Lys 65 70 75 atc cga att aagtgg acc aag cta act tcg gat tac ctc aag gaa gtg 591 Ile Arg Ile Lys TrpThr Lys Leu Thr Ser Asp Tyr Leu Lys Glu Val 80 85 90 gat gtt ttt gtt tccatg gga tac cac aaa aaa acc tat gga ggc tac 639 Asp Val Phe Val Ser MetGly Tyr His Lys Lys Thr Tyr Gly Gly Tyr 95 100 105 cag ggt aga gtg tttctg aag gga ggc agt gat agt gat gct tct ctg 687 Gln Gly Arg Val Phe LeuLys Gly Gly Ser Asp Ser Asp Ala Ser Leu 110 115 120 gtc atc aca gac ctcact ctg gaa gat tat ggg aga tat aag tgt gag 735 Val Ile Thr Asp Leu ThrLeu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu 125 130 135 140 gtg att gaa ggatta gaa gat gat act gtt gtg gta gca ctg gac tta 783 Val Ile Glu Gly LeuGlu Asp Asp Thr Val Val Val Ala Leu Asp Leu 145 150 155 caa ggt gtg gtattc cct tac ttt cca cga ctg ggg cgc tac aat ctc 831 Gln Gly Val Val PhePro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu 160 165 170 aat ttt cac gaggcg cag cag gcg tgt ctg gac cag gat gct gtg atc 879 Asn Phe His Glu AlaGln Gln Ala Cys Leu Asp Gln Asp Ala Val Ile 175 180 185 gcc tcc ttc gaccag ctg tac gac gcc tgg cgg ggc ggg ctg gac tgg 927 Ala Ser Phe Asp GlnLeu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp 190 195 200 tgc aat gcc ggctgg ctc agt gat ggc tct gtg caa tat ccc atc aca 975 Cys Asn Ala Gly TrpLeu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr 205 210 215 220 aag ccc agagag ccc tgt ggg ggc cag aac aca gtg ccc gga gtc agg 1023 Lys Pro Arg GluPro Cys Gly Gly Gln Asn Thr Val Pro Gly Val Arg 225 230 235 aac tac ggattt tgg gat aaa gat aaa agc aga tat gat gtt ttc tgt 1071 Asn Tyr Gly PheTrp Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys 240 245 250 ttt aca tccaat ttc aat ggc cgt ttt tac tat ctg atc cac ccc acc 1119 Phe Thr Ser AsnPhe Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr 255 260 265 aaa ctg acctat gat gaa gcg gtg caa gct tgt ctc aat gat ggt gct 1167 Lys Leu Thr TyrAsp Glu Ala Val Gln Ala Cys Leu Asn Asp Gly Ala 270 275 280 cag att gcaaaa gtg ggc cag ata ttt gct gcc tgg aaa att ctc gga 1215 Gln Ile Ala LysVal Gly Gln Ile Phe Ala Ala Trp Lys Ile Leu Gly 285 290 295 300 tat gaccgc tgt gat gcg ggc tgg ttg gcg gat ggc agc gtc cgc tac 1263 Tyr Asp ArgCys Asp Ala Gly Trp Leu Ala Asp Gly Ser Val Arg Tyr 305 310 315 ccc atctct agg cca aga agg cgc tgc agt cct act gag gct gca gtg 1311 Pro Ile SerArg Pro Arg Arg Arg Cys Ser Pro Thr Glu Ala Ala Val 320 325 330 cgc ttcgtg ggt ttc cca gat aaa aag cat aag ctg tat ggt gtc tac 1359 Arg Phe ValGly Phe Pro Asp Lys Lys His Lys Leu Tyr Gly Val Tyr 335 340 345 tgc ttcaga gca tac aac tga atgtgccctt agagcgcatc agttttaaag 1410 Cys Phe ArgAla Tyr Asn * 350 tcattaagaa catgtgaaag gtgttttttt tttccaatat gaactcatgcaagttaccaa 1470 aactgtgata accctttttt acttactgta aagagtcatt ttcataagatcaattcattg 1530 atttgttttt tgtaaagcta tcattcaata tatattataa attaatataaatttaaggga 1590 agctctatgt aaggagactt agagccaaac tgtttaagct gtatcatcccaacaaagtat 1650 cccttcatga acggggcatg caatagctta agaattgcta ggattaaattaaggaaagta 1710 aagctactca gagcaacagg ttccacaagc acaaacttta cacatttgtacaattttgaa 1770 atgcactaca ataaacaaat tagagcaaca catttgaaat acaggcttctttacataaac 1830 tgagaggtta tacaaaactc agtttcacaa gggaacaatc tatacctttctaaaagttaa 1890 tatttcaagt ctctaatagg cagaatattt tactctttaa aatcctgcctttctgaccaa 1950 aaaaaaa 1957 21 354 PRT Homo sapiens 21 Met Lys Ser LeuLeu Leu Leu Val Leu Ile Ser Ile Cys Trp Ala Asp 1 5 10 15 His Leu SerAsp Asn Tyr Thr Leu Asp His Asp Arg Ala Ile His Ile 20 25 30 Gln Ala GluAsn Gly Pro His Leu Leu Val Glu Ala Glu Gln Ala Lys 35 40 45 Val Phe SerHis Arg Gly Gly Asn Val Thr Leu Pro Cys Lys Phe Tyr 50 55 60 Arg Asp ProThr Ala Phe Gly Ser Gly Ile His Lys Ile Arg Ile Lys 65 70 75 80 Trp ThrLys Leu Thr Ser Asp Tyr Leu Lys Glu Val Asp Val Phe Val 85 90 95 Ser MetGly Tyr His Lys Lys Thr Tyr Gly Gly Tyr Gln Gly Arg Val 100 105 110 PheLeu Lys Gly Gly Ser Asp Ser Asp Ala Ser Leu Val Ile Thr Asp 115 120 125Leu Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu Val Ile Glu Gly 130 135140 Leu Glu Asp Asp Thr Val Val Val Ala Leu Asp Leu Gln Gly Val Val 145150 155 160 Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu Asn Phe HisGlu 165 170 175 Ala Gln Gln Ala Cys Leu Asp Gln Asp Ala Val Ile Ala SerPhe Asp 180 185 190 Gln Leu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp CysAsn Ala Gly 195 200 205 Trp Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile ThrLys Pro Arg Glu 210 215 220 Pro Cys Gly Gly Gln Asn Thr Val Pro Gly ValArg Asn Tyr Gly Phe 225 230 235 240 Trp Asp Lys Asp Lys Ser Arg Tyr AspVal Phe Cys Phe Thr Ser Asn 245 250 255 Phe Asn Gly Arg Phe Tyr Tyr LeuIle His Pro Thr Lys Leu Thr Tyr 260 265 270 Asp Glu Ala Val Gln Ala CysLeu Asn Asp Gly Ala Gln Ile Ala Lys 275 280 285 Val Gly Gln Ile Phe AlaAla Trp Lys Ile Leu Gly Tyr Asp Arg Cys 290 295 300 Asp Ala Gly Trp LeuAla Asp Gly Ser Val Arg Tyr Pro Ile Ser Arg 305 310 315 320 Pro Arg ArgArg Cys Ser Pro Thr Glu Ala Ala Val Arg Phe Val Gly 325 330 335 Phe ProAsp Lys Lys His Lys Leu Tyr Gly Val Tyr Cys Phe Arg Ala 340 345 350 TyrAsn 22 1957 DNA Homo sapiens CDS (316)...(1380) 22 ttaggctgta attaggggatttgggaggag aactttcctg gtgacgcttt gcttttcttc 60 tgctcttggt gagaaagtgcctccttcttc ccaggatcag gacctctgcc atccagcgcc 120 acaaagagac attctgcacacacactcaca cacacacaca cacacacact ctcacactcg 180 cccagagaca aacttaaggtgaggagaaag agcgctacgt tcacttgatc tccagcttcc 240 aacttaagca gaacttgagagcatccgaac tcctggattt caggacaagt gaagaagatt 300 ctttgggcta taaag atg aagagt cta ctt ctt ctg gtg ctg att tca atc 351 Met Lys Ser Leu Leu Leu LeuVal Leu Ile Ser Ile 1 5 10 tgc tgg gct gat cat ctt tca gac aac tat actctg gat cat gac aga 399 Cys Trp Ala Asp His Leu Ser Asp Asn Tyr Thr LeuAsp His Asp Arg 15 20 25 gct att cac atc caa gca gaa aat ggc ccc cat ctactt gtg gaa gca 447 Ala Ile His Ile Gln Ala Glu Asn Gly Pro His Leu LeuVal Glu Ala 30 35 40 gag caa gcc aag gtg ttt tca cac aga ggt ggc aat gttaca ctg cca 495 Glu Gln Ala Lys Val Phe Ser His Arg Gly Gly Asn Val ThrLeu Pro 45 50 55 60 tgt aaa ttt tat cga gac cct aca gca ttt ggc tca ggaatc cat aaa 543 Cys Lys Phe Tyr Arg Asp Pro Thr Ala Phe Gly Ser Gly IleHis Lys 65 70 75 atc cga att aag tgg acc aag cta act tcg gat tac ctc aaggaa gtg 591 Ile Arg Ile Lys Trp Thr Lys Leu Thr Ser Asp Tyr Leu Lys GluVal 80 85 90 gat gtt ttt gtt tcc atg gga tac cac aaa aaa acc tat gga ggctac 639 Asp Val Phe Val Ser Met Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr95 100 105 cag ggt aga gtg ttt ctg aag gga ggc agt gat agt gat gct tctctg 687 Gln Gly Arg Val Phe Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser Leu110 115 120 gtc atc aca gac ctc act ctg gaa gat tat ggg aga tat aag tgtgag 735 Val Ile Thr Asp Leu Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu125 130 135 140 gtg att gaa gga tta gaa gat gat act gtt gtg gta gca ctggac tta 783 Val Ile Glu Gly Leu Glu Asp Asp Thr Val Val Val Ala Leu AspLeu 145 150 155 caa ggt gtg gta ttc cct tac ttt cca cga ctg ggg cgc tacaat ctc 831 Gln Gly Val Val Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr AsnLeu 160 165 170 aat ttt cac gag gcg cag cag gcg tgt ctg gac cag gat gctgtg atc 879 Asn Phe His Glu Ala Gln Gln Ala Cys Leu Asp Gln Asp Ala ValIle 175 180 185 gcc tcc ttc gac cag ctg tac gac gcc tgg cgg ggc ggg ctggac tgg 927 Ala Ser Phe Asp Gln Leu Tyr Asp Ala Trp Arg Gly Gly Leu AspTrp 190 195 200 tgc aat gcc ggc tgg ctc agt gat ggc tct gtg caa tat cccatc aca 975 Cys Asn Ala Gly Trp Leu Ser Asp Gly Ser Val Gln Tyr Pro IleThr 205 210 215 220 aag ccc aga gag ccc tgt ggg ggc cag aac aca gtg cccgga gtc agg 1023 Lys Pro Arg Glu Pro Cys Gly Gly Gln Asn Thr Val Pro GlyVal Arg 225 230 235 aac tac gga ttt tgg gat aaa gat aaa agc aga tat gatgtt ttc tgt 1071 Asn Tyr Gly Phe Trp Asp Lys Asp Lys Ser Arg Tyr Asp ValPhe Cys 240 245 250 ttt aca tcc aat ttc aat ggc cgt ttt tac tat ctg atccac ccc acc 1119 Phe Thr Ser Asn Phe Asn Gly Arg Phe Tyr Tyr Leu Ile HisPro Thr 255 260 265 aaa ctg acc tat gat gaa gcg gtg caa gct tgt ctc aatgat ggt gct 1167 Lys Leu Thr Tyr Asp Glu Ala Val Gln Ala Cys Leu Asn AspGly Ala 270 275 280 cag att gca aaa gtg ggc cag ata ttt gct gcc tgg aaaatt ctc gga 1215 Gln Ile Ala Lys Val Gly Gln Ile Phe Ala Ala Trp Lys IleLeu Gly 285 290 295 300 tat gac cgc tgt gat gcg ggc tgg ttg gcg gat ggcagc gtc cgc tac 1263 Tyr Asp Arg Cys Asp Ala Gly Trp Leu Ala Asp Gly SerVal Arg Tyr 305 310 315 ccc atc tct agg cca aga agg cgc tgc agt cct actgag gct gca gtg 1311 Pro Ile Ser Arg Pro Arg Arg Arg Cys Ser Pro Thr GluAla Ala Val 320 325 330 cgc ttc gtg ggt ttc cca gat aaa aag cat aag ctgtat ggt gtc tac 1359 Arg Phe Val Gly Phe Pro Asp Lys Lys His Lys Leu TyrGly Val Tyr 335 340 345 tgc ttc aga gca tac aac tga atgtgcccttagagcgcatc agttttaaag 1410 Cys Phe Arg Ala Tyr Asn * 350 tcattaagaacatgtgaaag gtgttttttt tttccaatat gaactcatgc aagttaccaa 1470 aactgtgataaccctttttt acttactgta aagagtcatt ttcataagat caattcattg 1530 atttgttttttgtaaagcta tcattcaata tatattataa attaatataa atttaaggga 1590 agctctatgtaaggagactt agagccaaac tgtttaagct gtatcatccc aacaaagtat 1650 cctttcatgaacggggcatg caatagctta agaattgcta ggattaaatt aaggaaagta 1710 aagctactcagagcagcagg ttccacaagc acaaacttta cacatttgta caattttgaa 1770 atgcactacaataaacaaat tagagcaaca catttgaaat acaggcttct ttacataaac 1830 tgagaggttatacaaaactc agtttcacaa gggaacaatc tatacctttc taaaagttaa 1890 tatttcaagtctctaatagg cagaatattt tactctttaa aatcctgcct ttctgaccaa 1950 aaaaaaa 195723 354 PRT Homo sapiens 23 Met Lys Ser Leu Leu Leu Leu Val Leu Ile SerIle Cys Trp Ala Asp 1 5 10 15 His Leu Ser Asp Asn Tyr Thr Leu Asp HisAsp Arg Ala Ile His Ile 20 25 30 Gln Ala Glu Asn Gly Pro His Leu Leu ValGlu Ala Glu Gln Ala Lys 35 40 45 Val Phe Ser His Arg Gly Gly Asn Val ThrLeu Pro Cys Lys Phe Tyr 50 55 60 Arg Asp Pro Thr Ala Phe Gly Ser Gly IleHis Lys Ile Arg Ile Lys 65 70 75 80 Trp Thr Lys Leu Thr Ser Asp Tyr LeuLys Glu Val Asp Val Phe Val 85 90 95 Ser Met Gly Tyr His Lys Lys Thr TyrGly Gly Tyr Gln Gly Arg Val 100 105 110 Phe Leu Lys Gly Gly Ser Asp SerAsp Ala Ser Leu Val Ile Thr Asp 115 120 125 Leu Thr Leu Glu Asp Tyr GlyArg Tyr Lys Cys Glu Val Ile Glu Gly 130 135 140 Leu Glu Asp Asp Thr ValVal Val Ala Leu Asp Leu Gln Gly Val Val 145 150 155 160 Phe Pro Tyr PhePro Arg Leu Gly Arg Tyr Asn Leu Asn Phe His Glu 165 170 175 Ala Gln GlnAla Cys Leu Asp Gln Asp Ala Val Ile Ala Ser Phe Asp 180 185 190 Gln LeuTyr Asp Ala Trp Arg Gly Gly Leu Asp Trp Cys Asn Ala Gly 195 200 205 TrpLeu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr Lys Pro Arg Glu 210 215 220Pro Cys Gly Gly Gln Asn Thr Val Pro Gly Val Arg Asn Tyr Gly Phe 225 230235 240 Trp Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys Phe Thr Ser Asn245 250 255 Phe Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr Lys Leu ThrTyr 260 265 270 Asp Glu Ala Val Gln Ala Cys Leu Asn Asp Gly Ala Gln IleAla Lys 275 280 285 Val Gly Gln Ile Phe Ala Ala Trp Lys Ile Leu Gly TyrAsp Arg Cys 290 295 300 Asp Ala Gly Trp Leu Ala Asp Gly Ser Val Arg TyrPro Ile Ser Arg 305 310 315 320 Pro Arg Arg Arg Cys Ser Pro Thr Glu AlaAla Val Arg Phe Val Gly 325 330 335 Phe Pro Asp Lys Lys His Lys Leu TyrGly Val Tyr Cys Phe Arg Ala 340 345 350 Tyr Asn 24 354 PRT Homo sapiens24 Met Lys Ser Leu Leu Leu Leu Val Leu Ile Ser Ile Cys Trp Ala Asp 1 510 15 His Leu Ser Asp Asn Tyr Thr Leu Asp His Asp Arg Ala Ile His Ile 2025 30 Gln Ala Glu Asn Gly Pro His Leu Leu Val Glu Ala Glu Gln Ala Lys 3540 45 Val Phe Ser His Arg Gly Gly Asn Val Thr Leu Pro Cys Lys Phe Tyr 5055 60 Arg Asp Pro Thr Ala Phe Gly Ser Gly Ile His Lys Ile Arg Ile Lys 6570 75 80 Trp Thr Lys Leu Thr Ser Asp Tyr Leu Lys Glu Val Asp Val Phe Val85 90 95 Ser Met Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr Gln Gly Arg Val100 105 110 Phe Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser Leu Val Ile ThrAsp 115 120 125 Leu Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu Val IleGlu Gly 130 135 140 Leu Glu Asp Asp Thr Val Val Val Ala Leu Asp Leu GlnGly Val Val 145 150 155 160 Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr AsnLeu Asn Phe His Glu 165 170 175 Ala Gln Gln Ala Cys Leu Asp Gln Asp AlaVal Ile Ala Ser Phe Asp 180 185 190 Gln Leu Tyr Asp Ala Trp Arg Gly GlyLeu Asp Trp Cys Asn Ala Gly 195 200 205 Trp Leu Ser Asp Gly Ser Val GlnTyr Pro Ile Thr Lys Pro Arg Glu 210 215 220 Pro Cys Gly Gly Gln Asn ThrVal Pro Gly Val Arg Asn Tyr Gly Phe 225 230 235 240 Trp Asp Lys Asp LysSer Arg Tyr Asp Val Phe Cys Phe Thr Ser Asn 245 250 255 Phe Asn Gly ArgPhe Tyr Tyr Leu Ile His Pro Thr Lys Leu Thr Tyr 260 265 270 Asp Glu AlaVal Gln Ala Cys Leu Asn Asp Gly Ala Gln Ile Ala Lys 275 280 285 Val GlyGln Ile Phe Ala Ala Trp Lys Ile Leu Gly Tyr Asp Arg Cys 290 295 300 AspAla Gly Trp Leu Ala Asp Gly Ser Val Arg Tyr Pro Ile Ser Arg 305 310 315320 Pro Arg Arg Arg Cys Ser Pro Thr Glu Ala Ala Val Arg Phe Val Gly 325330 335 Phe Pro Asp Lys Lys His Lys Leu Tyr Gly Val Tyr Cys Phe Arg Ala340 345 350 Tyr Asn 25 721 PRT Homo sapiens 25 Met Leu Glu His Thr ThrLys Thr Phe Pro Leu Arg Ala Leu His Ile 1 5 10 15 Val Val Glu Ser IleArg Asp His Ser Gly Gln Lys Met Lys Gln Asp 20 25 30 Lys Lys Val Asp LeuLeu Val Pro Thr Lys Val Thr Gly Ile Ile Thr 35 40 45 Gln Gly Ala Lys AspPhe Gly His Val Gln Phe Val Gly Ser Tyr Lys 50 55 60 Leu Ala Tyr Ser AsnAsp Gly Glu His Trp Thr Val Tyr Gln Asp Glu 65 70 75 80 Lys Gln Arg LysAsp Lys Val Leu Leu Gly Arg Lys Ala Val Val Val 85 90 95 Ser Cys Glu GlyIle Asn Ile Ser Gly Ser Phe Cys Arg Asn Lys Leu 100 105 110 Lys Tyr LeuAla Phe Leu His Lys Arg Met Asn Thr Asn Pro Ser Arg 115 120 125 Arg ProTyr His Phe Gln Val Pro Ser Arg Ile Phe Trp Arg Gln Glu 130 135 140 LysAla Asp Gly Gly Ser Cys Cys Pro Gln Gly His Ala Ser Glu Ala 145 150 155160 Tyr Lys Lys Val Cys Leu Ser Gly Ala Pro His Glu Val Gly Trp Lys 165170 175 Tyr Gln Ala Val Thr Ala Thr Leu Glu Glu Lys Arg Lys Glu Lys Ala180 185 190 Glu Ile His Tyr Arg Lys Asn Lys Gln Leu Met Arg Leu Gln LysGln 195 200 205 Ala Glu Lys Asn Met Lys Lys Lys Ile Asp Lys Tyr Thr GluSer Pro 210 215 220 Gly Gly Gly Ser Pro Arg Gly Leu Gly Phe Ile Phe LysThr Ile Ala 225 230 235 240 Pro Leu Ala Ala Thr Arg Ala Thr Arg Ile GlyHis Pro Gly Gly Arg 245 250 255 Thr Pro Arg Ala Gly Ser Ser Ala His ArgPro Pro Ala Leu Ser Ala 260 265 270 Arg Ala Pro Val Pro Ala Ala Ser ProAla Ala Trp Leu Pro Leu Arg 275 280 285 Thr Pro Trp Thr Arg Pro Ser SerCys Pro Thr Ser Ser Ser Thr Tyr 290 295 300 Asp Ser Leu Ser Pro Tyr GlyPro Arg Asn Pro Leu Pro Asn Pro Arg 305 310 315 320 His Ser Pro Ser GlyGly Gly Gly Leu Lys Lys Pro Ala Arg His Cys 325 330 335 Gln Gly Gln LysHis Asn Val Leu Ala Arg Gly Lys Pro Gln Arg Lys 340 345 350 Pro Lys SerGlu Asn Asn Ser Trp Tyr Val Glu Asn Gly Arg Pro Ala 355 360 365 Asp LeuAla Gly Ser Gly Tyr Cys Gly Ala Leu Trp Lys Ala Ile Glu 370 375 380 SerLeu Glu Glu Gly Leu Gly Gly Lys Gln Lys Asp Lys Glu Arg Lys 385 390 395400 Ala Glu Asn Gly Pro His Leu Leu Val Glu Ala Glu Gln Ala Lys Val 405410 415 Phe Ser His Arg Gly Gly Asn Val Thr Leu Pro Cys Lys Phe Tyr Arg420 425 430 Asp Pro Thr Ala Phe Gly Ser Gly Ile His Lys Ile Arg Ile LysTrp 435 440 445 Thr Lys Leu Thr Ser Asp Tyr Leu Lys Glu Val Asp Val PheVal Ser 450 455 460 Met Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr Gln GlyArg Val Phe 465 470 475 480 Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser LeuVal Ile Thr Asp Leu 485 490 495 Thr Leu Glu Asp Tyr Gly Arg Tyr Lys CysGlu Val Ile Glu Gly Leu 500 505 510 Glu Asp Asp Thr Val Val Val Ala LeuAsp Leu Gln Gly Val Val Phe 515 520 525 Pro Tyr Phe Pro Arg Leu Gly ArgTyr Asn Leu Asn Phe His Glu Ala 530 535 540 Gln Gln Ala Cys Leu Asp GlnAsp Ala Val Ile Ala Ser Phe Asp Gln 545 550 555 560 Leu Tyr Asp Ala TrpArg Gly Gly Leu Asp Trp Cys Asn Ala Gly Trp 565 570 575 Leu Ser Asp GlySer Val Gln Tyr Pro Ile Thr Lys Pro Arg Glu Pro 580 585 590 Cys Gly GlyGln Asn Thr Val Pro Gly Val Arg Asn Tyr Gly Phe Trp 595 600 605 Asp LysAsp Lys Ser Arg Tyr Asp Val Phe Cys Phe Thr Ser Asn Phe 610 615 620 AsnGly Arg Phe Tyr Tyr Leu Ile His Pro Thr Lys Leu Thr Tyr Asp 625 630 635640 Glu Ala Val Gln Ala Cys Leu Asn Asp Gly Ala Gln Ile Ala Lys Val 645650 655 Gly Gln Ile Phe Ala Ala Trp Lys Ile Leu Gly Tyr Asp Arg Cys Asp660 665 670 Ala Gly Trp Leu Ala Asp Gly Ser Val Arg Tyr Pro Ile Ser ArgPro 675 680 685 Arg Arg Arg Cys Ser Pro Thr Glu Ala Ala Val Arg Phe ValGly Phe 690 695 700 Pro Asp Lys Lys His Lys Leu Tyr Gly Val Tyr Cys PheArg Ala Tyr 705 710 715 720 Asn 26 1957 DNA Homo sapiens 26 ttaggctgtaattaggggat ttgggaggag aactttcctg gtgacgcttt gcttttcttc 60 tgctcttggtgagaaagtgc ctccttcttc ccaggatcag gacctctgcc atccagcgcc 120 acaaagagacattctgcaca cacactcaca cacacacaca cacacacact ctcacactcg 180 cccagagacaaacttaaggt gaggagaaag agcgctacgt tcacttgatc tccagcttcc 240 aacttaagcagaacttgaga gcatccgaac tcctggattt caggacaagt gaagaagatt 300 ctttgggctataaagatgaa gagtctactt cttctggtgc tgatttcaat ctgctgggct 360 gatcatctttcagacaacta tactctggat catgacagag ctattcacat ccaagcagaa 420 aatggcccccatctacttgt ggaagcagag caagccaagg tgttttcaca cagaggtggc 480 aatgttacactgccatgtaa attttatcga gaccctacag catttggctc aggaatccat 540 aaaatccgaattaagtggac caagctaact tcggattacc tcaaggaagt ggatgttttt 600 gtttccatgggataccacaa aaaaacctat ggaggctacc agggtagagt gtttctgaag 660 ggaggcagtgatagtgatgc ttctctggtc atcacagacc tcactctgga agattatggg 720 agatataagtgtgaggtgat tgaaggatta gaagatgata ctgttgtggt agcactggac 780 ttacaaggtgtggtattccc ttactttcca cgactggggc gctacaatct caattttcac 840 gaggcgcagcaggcgtgtct ggaccaggat gctgtgatcg cctccttcga ccagctgtac 900 gacgcctggcggggcgggct ggactggtgc aatgccggct ggctcagtga tggctctgtg 960 caatatcccatcacaaagcc cagagagccc tgtgggggcc agaacacagt gcccggagtc 1020 aggaactacggattttggga taaagataaa agcagatatg atgttttctg ttttacatcc 1080 aatttcaatggccgttttta ctatctgatc caccccacca aactgaccta tgatgaagcg 1140 gtgcaagcttgtctcaatga tggtgctcag attgcaaaag tgggccagat atttgctgcc 1200 tggaaaattctcggatatga ccgctgtgat gcgggctggt tggcggatgg cagcgtccgc 1260 taccccatctctaggccaag aaggcgctgc agtcctactg aggctgcagt gcgcttcgtg 1320 ggtttcccagataaaaagca taagctgtat ggtgtctact gcttcagagc atacaactga 1380 atgtgcccttagagcgcatc agttttaaag tcattaagaa catgtgaaag gtgttttttt 1440 tttccaatatgaactcatgc aagttaccaa aactgtgata accctttttt acttactgta 1500 aagagtcattttcataagat caattcattg atttgttttt tgtaaagcta tcattcaata 1560 tatattataaattaatataa atttaaggga agctctatgt aaggagactt agagccaaac 1620 tgtttaagctgtatcatccc aacaaagtat cctttcatga acggggcatg caatagctta 1680 agaattgctaggattaaatt aaggaaagta aagctactca gagcaacagg ttccacaagc 1740 acaaactttacacatttgta caattttgaa atgcactaca ataaacaaat tagagcaaca 1800 catttgaaatacaggcttct ttacataaac tgagaggtta tacaaaactc agtttcacaa 1860 gggaacaatctatacctttc taaaagttaa tatttcaagt ctctaatagg cagaatattt 1920 tactctttaaaatcctgcct ttctgaccaa aaaaaaa 1957 27 1492 DNA Homo sapiens 27ttaggctgta attaggggat ttgggaggag aactttcctg gtgacgcttt gcttttcttc 60tgctcttggt gagaaagtgc ctccttcttc ccaggatcag gacctctgcc atccagcgcc 120acaaagagac attctgcaca cacactcaca cacacacaca cacacacact ctcacactcg 180cccagagaca aacttaaggt gaggagaaag agcgctagct tcacttgatc tccagcttcc 240aacttaagca gaacttgaga gcatccgaac tcctggattt caggacaagt gaagaagatt 300ctttgggcta taaagatgaa gagtctactt cttctggtgc tgatttcaat ctgctgggct 360gatcatcttt cagacaacta tactctggat catgacagag ctattcacat ccaagcagaa 420aatggccccc atctacttgt ggaagcagag caagccaagg tgttttcaca cagaggtggc 480aatgttacac tgccatgtaa attttatcga gaccctacag catttggctc aggaatccat 540aaaatccgaa ttaagtggac caagctaact tcggattacc tcaaggaagt ggatgttttt 600gtttccatgg gataccacaa aaaaacctat ggaggctacc agggtagagt gtttctgaag 660ggaggcagtg atagtgatgc ttctctggtc atcacagacc tcactctgga agattatggg 720agatataagt gtgaggtgat tgaaggatta gaagatgata ctgttgtggt agcactggac 780ttacaaggtg tggtattccc ttactttcca cgactggggc gctacaatct caattttcac 840gaggcgcagc aggcgtgtct ggaccaggat gctgtgatcg cctccttcga ccagctgtac 900gacgcctggc ggggcgggct ggactggtgc aatgccggct ggctcagtga tggctctgtg 960caatatccca tcacaaagcc cagagagccc tgtgggggcc agaacacagt gcccggagtc 1020aggaactacg gattttggga taaagataaa agcagatatg atgttttctg ttttacatcc 1080aatttcaatg gccgttttta ctatctgatc caccccacca aactgaccta tgatgaagcg 1140gtgcaagctt gtctcaatga tggtgctcag attgcaaaag tgggccagat atttgctgcc 1200tggaaaattc tcggatatga ccgctgtgat gcgggctggt tggcggatgg cagcgtccgc 1260taccccatct ctaggccaag aaggcgctgc agtcctactg aggctgcagt gcgcttcgtg 1320ggttttccag ataaaaagca taagctgtat ggtgtctact gcttcagagc atacaactga 1380atgtgccctt agagcgcact agttttaaag tcattaagaa catgtgaaag gtgttttttt 1440tttccaatat gaactcatgc aagttaccaa aactgtgata accctttttt ac 1492 28 354PRT Homo sapiens 28 Met Lys Ser Leu Leu Leu Leu Val Leu Ile Ser Ile CysTrp Ala Asp 1 5 10 15 His Leu Ser Asp Asn Tyr Thr Leu Asp His Asp ArgAla Ile His Ile 20 25 30 Gln Ala Glu Asn Gly Pro His Leu Leu Val Glu AlaGlu Gln Ala Lys 35 40 45 Val Phe Ser His Arg Gly Gly Asn Val Thr Leu ProCys Lys Phe Tyr 50 55 60 Arg Asp Pro Thr Ala Phe Gly Ser Gly Ile His LysIle Arg Ile Lys 65 70 75 80 Trp Thr Lys Leu Thr Ser Asp Tyr Leu Lys GluVal Asp Val Phe Val 85 90 95 Ser Met Gly Tyr His Lys Lys Thr Tyr Gly GlyTyr Gln Gly Arg Val 100 105 110 Phe Leu Lys Gly Gly Ser Asp Ser Asp AlaSer Leu Val Ile Thr Asp 115 120 125 Leu Thr Leu Glu Asp Tyr Gly Arg TyrLys Cys Glu Val Ile Glu Gly 130 135 140 Leu Glu Asp Asp Thr Val Val ValAla Leu Asp Leu Gln Gly Val Val 145 150 155 160 Phe Pro Tyr Phe Pro ArgLeu Gly Arg Tyr Asn Leu Asn Phe His Glu 165 170 175 Ala Gln Gln Ala CysLeu Asp Gln Asp Ala Val Ile Ala Ser Phe Asp 180 185 190 Gln Leu Tyr AspAla Trp Arg Gly Gly Leu Asp Trp Cys Asn Ala Gly 195 200 205 Trp Leu SerAsp Gly Ser Val Gln Tyr Pro Ile Thr Lys Pro Arg Glu 210 215 220 Pro CysGly Gly Gln Asn Thr Val Pro Gly Val Arg Asn Tyr Gly Phe 225 230 235 240Trp Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys Phe Thr Ser Asn 245 250255 Phe Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr Lys Leu Thr Tyr 260265 270 Asp Glu Ala Val Gln Ala Cys Leu Asn Asp Gly Ala Gln Ile Ala Lys275 280 285 Val Gly Gln Ile Phe Ala Ala Trp Lys Ile Leu Gly Tyr Asp ArgCys 290 295 300 Asp Ala Gly Trp Leu Ala Asp Gly Ser Val Arg Tyr Pro IleSer Arg 305 310 315 320 Pro Arg Arg Arg Cys Ser Pro Thr Glu Ala Ala ValArg Phe Val Gly 325 330 335 Phe Pro Asp Lys Lys His Lys Leu Tyr Gly ValTyr Cys Phe Arg Ala 340 345 350 Tyr Asn 29 354 PRT Homo sapiens 29 MetLys Ser Leu Leu Leu Leu Val Leu Ile Ser Ile Cys Trp Ala Asp 1 5 10 15His Leu Ser Asp Asn Tyr Thr Leu Asp His Asp Arg Ala Ile His Ile 20 25 30Gln Ala Glu Asn Gly Pro His Leu Leu Val Glu Ala Glu Gln Ala Lys 35 40 45Val Phe Ser His Arg Gly Gly Asn Val Thr Leu Pro Cys Lys Phe Tyr 50 55 60Arg Asp Pro Thr Ala Phe Gly Ser Gly Ile His Lys Ile Arg Ile Lys 65 70 7580 Trp Thr Lys Leu Thr Ser Asp Tyr Leu Lys Glu Val Asp Val Phe Val 85 9095 Ser Met Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr Gln Gly Arg Val 100105 110 Phe Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser Leu Val Ile Thr Asp115 120 125 Leu Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu Val Ile GluGly 130 135 140 Leu Glu Asp Asp Thr Val Val Val Ala Leu Asp Leu Gln GlyVal Val 145 150 155 160 Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn LeuAsn Phe His Glu 165 170 175 Ala Gln Gln Ala Cys Leu Asp Gln Asp Ala ValIle Ala Ser Phe Asp 180 185 190 Gln Leu Tyr Asp Ala Trp Arg Gly Gly LeuAsp Trp Cys Asn Ala Gly 195 200 205 Trp Leu Ser Asp Gly Ser Val Gln TyrPro Ile Thr Lys Pro Arg Glu 210 215 220 Pro Cys Gly Gly Gln Asn Thr ValPro Gly Val Arg Asn Tyr Gly Phe 225 230 235 240 Trp Asp Lys Asp Lys SerArg Tyr Asp Val Phe Cys Phe Thr Ser Asn 245 250 255 Phe Asn Gly Arg PheTyr Tyr Leu Ile His Pro Thr Lys Leu Thr Tyr 260 265 270 Asp Glu Ala ValGln Ala Cys Leu Asn Asp Gly Ala Gln Ile Ala Lys 275 280 285 Val Gly GlnIle Phe Ala Ala Trp Lys Ile Leu Gly Tyr Asp Arg Cys 290 295 300 Asp AlaGly Trp Leu Ala Asp Gly Ser Val Arg Tyr Pro Ile Ser Arg 305 310 315 320Pro Arg Arg Arg Cys Ser Pro Thr Glu Ala Ala Val Arg Phe Val Gly 325 330335 Phe Pro Asp Lys Lys His Lys Leu Tyr Gly Val Tyr Cys Phe Arg Ala 340345 350 Tyr Asn 30 354 PRT Homo sapiens 30 Met Lys Ser Leu Leu Leu LeuVal Leu Ile Ser Ile Cys Trp Ala Asp 1 5 10 15 His Leu Ser Asp Asn TyrThr Leu Asp His Asp Arg Ala Ile His Ile 20 25 30 Gln Ala Glu Asn Gly ProHis Leu Leu Val Glu Ala Glu Gln Ala Lys 35 40 45 Val Phe Ser His Arg GlyGly Asn Val Thr Leu Pro Cys Lys Phe Tyr 50 55 60 Arg Asp Pro Thr Ala PheGly Ser Gly Ile His Lys Ile Arg Ile Lys 65 70 75 80 Trp Thr Lys Leu ThrSer Asp Tyr Leu Lys Glu Val Asp Val Phe Val 85 90 95 Ser Met Gly Tyr HisLys Lys Thr Tyr Gly Gly Tyr Gln Gly Arg Val 100 105 110 Phe Leu Lys GlyGly Ser Asp Ser Asp Ala Ser Leu Val Ile Thr Asp 115 120 125 Leu Thr LeuGlu Asp Tyr Gly Arg Tyr Lys Cys Glu Val Ile Glu Gly 130 135 140 Leu GluAsp Asp Thr Val Val Val Ala Leu Asp Leu Gln Gly Val Val 145 150 155 160Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu Asn Phe His Glu 165 170175 Ala Gln Gln Ala Cys Leu Asp Gln Asp Ala Val Ile Ala Ser Phe Asp 180185 190 Gln Leu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp Cys Asn Ala Gly195 200 205 Trp Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr Lys Pro ArgGlu 210 215 220 Pro Cys Gly Gly Gln Asn Thr Val Pro Gly Val Arg Asn TyrGly Phe 225 230 235 240 Trp Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe CysPhe Thr Ser Asn 245 250 255 Phe Asn Gly Arg Phe Tyr Tyr Leu Ile His ProThr Lys Leu Thr Tyr 260 265 270 Asp Glu Ala Val Gln Ala Cys Leu Asn AspGly Ala Gln Ile Ala Lys 275 280 285 Val Gly Gln Ile Phe Ala Ala Trp LysIle Leu Gly Tyr Asp Arg Cys 290 295 300 Asp Ala Gly Trp Leu Ala Asp GlySer Val Arg Tyr Pro Ile Ser Arg 305 310 315 320 Pro Arg Arg Arg Cys SerPro Thr Glu Ala Ala Val Arg Phe Val Gly 325 330 335 Phe Pro Asp Lys LysHis Lys Leu Tyr Gly Val Tyr Cys Phe Arg Ala 340 345 350 Tyr Asn 31 355PRT Mus musculus 31 Met Arg Ser Leu Leu Leu Leu Val Leu Ile Ser Val CysTrp Ala Asp 1 5 10 15 His Leu Ser Asp Ser Tyr Thr Pro Pro Asp Gln AspArg Val Ile His 20 25 30 Ile Gln Ala Glu Asn Gly Pro Arg Leu Leu Val GluAla Glu Gln Ala 35 40 45 Lys Val Phe Ser His Arg Gly Gly Asn Val Thr LeuPro Cys Lys Phe 50 55 60 Tyr Arg Asp Pro Thr Ala Phe Gly Ser Gly Ile HisLys Ile Arg Ile 65 70 75 80 Lys Trp Thr Lys Leu Thr Ser Asp Tyr Leu ArgGlu Val Asp Val Phe 85 90 95 Val Ser Met Gly Tyr His Lys Lys Thr Tyr GlyGly Tyr Gln Gly Arg 100 105 110 Val Phe Leu Lys Gly Gly Ser Asp Asn AspAla Ser Leu Val Ile Thr 115 120 125 Asp Leu Thr Leu Glu Asp Tyr Gly ArgTyr Lys Cys Glu Val Ile Glu 130 135 140 Gly Leu Glu Asp Asp Thr Ala ValVal Ala Leu Glu Leu Gln Gly Val 145 150 155 160 Val Phe Pro Tyr Phe ProArg Leu Gly Arg Tyr Asn Leu Asn Phe His 165 170 175 Glu Ala Arg Gln AlaCys Leu Asp Gln Asp Ala Val Ile Ala Ser Phe 180 185 190 Asp Gln Leu TyrAsp Ala Trp Arg Gly Gly Leu Asp Trp Cys Asn Ala 195 200 205 Gly Trp LeuSer Asp Gly Ser Val Gln Tyr Pro Ile Thr Lys Pro Arg 210 215 220 Glu ProCys Gly Gly Gln Asn Thr Val Pro Gly Val Arg Asn Tyr Gly 225 230 235 240Phe Trp Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys Phe Thr Ser 245 250255 Asn Phe Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr Lys Leu Thr 260265 270 Tyr Asp Glu Ala Val Gln Ala Cys Leu Asn Asp Gly Ala Gln Ile Ala275 280 285 Lys Val Gly Gln Ile Phe Ala Ala Trp Lys Leu Leu Gly Tyr AspArg 290 295 300 Cys Asp Ala Gly Trp Leu Ala Asp Gly Ser Val Arg Tyr ProIle Ser 305 310 315 320 Arg Pro Arg Arg Arg Cys Ser Pro Thr Glu Ala AlaVal Arg Phe Val 325 330 335 Gly Phe Pro Asp Lys Lys His Lys Leu Tyr GlyVal Tyr Cys Phe Arg 340 345 350 Ala Tyr Asn 355 32 322 PRT Homo sapiens32 Gln Ala Glu Asn Gly Pro His Leu Leu Val Glu Ala Glu Gln Ala Lys 1 510 15 Val Phe Ser His Arg Gly Gly Asn Val Thr Leu Pro Cys Lys Phe Tyr 2025 30 Arg Asp Pro Thr Ala Phe Gly Ser Gly Ile His Lys Ile Arg Ile Lys 3540 45 Trp Thr Lys Leu Thr Ser Asp Tyr Leu Lys Glu Val Asp Val Phe Val 5055 60 Ser Met Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr Gln Gly Arg Val 6570 75 80 Phe Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser Leu Val Ile Thr Asp85 90 95 Leu Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu Val Ile Glu Gly100 105 110 Leu Glu Asp Asp Thr Val Val Val Ala Leu Asp Leu Gln Gly ValVal 115 120 125 Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu Asn PheHis Glu 130 135 140 Ala Gln Gln Ala Cys Leu Asp Gln Asp Ala Val Ile AlaSer Phe Asp 145 150 155 160 Gln Leu Tyr Asp Ala Trp Arg Gly Gly Leu AspTrp Cys Asn Ala Gly 165 170 175 Trp Leu Ser Asp Gly Ser Val Gln Tyr ProIle Thr Lys Pro Arg Glu 180 185 190 Pro Cys Gly Gly Gln Asn Thr Val ProGly Val Arg Asn Tyr Gly Phe 195 200 205 Trp Asp Lys Asp Lys Ser Arg TyrAsp Val Phe Cys Phe Thr Ser Asn 210 215 220 Phe Asn Gly Arg Phe Tyr TyrLeu Ile His Pro Thr Lys Leu Thr Tyr 225 230 235 240 Asp Glu Ala Val GlnAla Cys Leu Asn Asp Gly Ala Gln Ile Ala Lys 245 250 255 Val Gly Gln IlePhe Ala Ala Trp Lys Ile Leu Gly Tyr Asp Arg Cys 260 265 270 Asp Ala GlyTrp Leu Ala Asp Gly Ser Val Arg Tyr Pro Ile Ser Arg 275 280 285 Pro ArgArg Arg Cys Ser Pro Thr Glu Ala Ala Val Arg Phe Val Gly 290 295 300 PhePro Asp Lys Lys His Lys Leu Tyr Gly Val Tyr Cys Phe Arg Ala 305 310 315320 Tyr Asn 33 322 PRT Homo sapiens 33 Lys Ala Glu Asn Gly Pro His LeuLeu Val Glu Ala Glu Gln Ala Lys 1 5 10 15 Val Phe Ser His Arg Gly GlyAsn Val Thr Leu Pro Cys Lys Phe Tyr 20 25 30 Arg Asp Pro Thr Ala Phe GlySer Gly Ile His Lys Ile Arg Ile Lys 35 40 45 Trp Thr Lys Leu Thr Ser AspTyr Leu Lys Glu Val Asp Val Phe Val 50 55 60 Ser Met Gly Tyr His Lys LysThr Tyr Gly Gly Tyr Gln Gly Arg Val 65 70 75 80 Phe Leu Lys Gly Gly SerAsp Ser Asp Ala Ser Leu Val Ile Thr Asp 85 90 95 Leu Thr Leu Glu Asp TyrGly Arg Tyr Lys Cys Glu Val Ile Glu Gly 100 105 110 Leu Glu Asp Asp ThrVal Val Val Ala Leu Asp Leu Gln Gly Val Val 115 120 125 Phe Pro Tyr PhePro Arg Leu Gly Arg Tyr Asn Leu Asn Phe His Glu 130 135 140 Ala Gln GlnAla Cys Leu Asp Gln Asp Ala Val Ile Ala Ser Phe Asp 145 150 155 160 GlnLeu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp Cys Asn Ala Gly 165 170 175Trp Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr Lys Pro Arg Glu 180 185190 Pro Cys Gly Gly Gln Asn Thr Val Pro Gly Val Arg Asn Tyr Gly Phe 195200 205 Trp Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys Phe Thr Ser Asn210 215 220 Phe Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr Lys Leu ThrTyr 225 230 235 240 Asp Glu Ala Val Gln Ala Cys Leu Asn Asp Gly Ala GlnIle Ala Lys 245 250 255 Val Gly Gln Ile Phe Ala Ala Trp Lys Ile Leu GlyTyr Asp Arg Cys 260 265 270 Asp Ala Gly Trp Leu Ala Asp Gly Ser Val ArgTyr Pro Ile Ser Arg 275 280 285 Pro Arg Arg Arg Cys Ser Pro Thr Glu AlaAla Val Arg Phe Val Gly 290 295 300 Phe Pro Asp Lys Lys His Lys Leu TyrGly Val Tyr Cys Phe Arg Ala 305 310 315 320 Tyr Asn 34 168 PRT Homosapiens 34 Met Asn Thr Asn Pro Ser Arg Arg Pro Tyr His Phe Gln Val ProSer 1 5 10 15 Arg Ile Phe Trp Arg Gln Glu Lys Ala Asp Gly Gly Ser CysCys Pro 20 25 30 Gln Gly His Ala Ser Glu Ala Tyr Lys Lys Val Cys Leu SerGly Ala 35 40 45 Pro His Glu Val Gly Trp Lys Tyr Gln Ala Val Thr Ala ThrLeu Glu 50 55 60 Glu Lys Arg Lys Glu Lys Ala Glu Ile His Tyr Arg Lys AsnLys Gln 65 70 75 80 Leu Met Arg Leu Gln Lys Gln Ala Glu Lys Asn Met LysLys Lys Ile 85 90 95 Asp Lys Tyr Thr Glu Ser Pro Gly Gly Gly Ser Pro ArgGly Leu Gly 100 105 110 Phe Ile Phe Lys Thr Ile Ala Pro Leu Ala Ala ThrArg Ala Thr Arg 115 120 125 Ile Gly His Pro Gly Gly Arg Thr Pro Arg AlaGly Ser Ser Ala His 130 135 140 Arg Pro Pro Ala Leu Ser Ala Arg Ala ProVal Pro Ala Ala Ser Pro 145 150 155 160 Ala Ala Trp Leu Pro Leu Arg Thr165 35 168 PRT Homo sapiens 35 Met Asn Thr Asn Pro Ser Arg Arg Pro TyrHis Phe Gln Val Pro Ser 1 5 10 15 Arg Ile Phe Trp Arg Gln Glu Lys AlaAsp Gly Gly Ser Cys Cys Pro 20 25 30 Gln Gly His Ala Ser Glu Ala Tyr LysLys Val Cys Leu Ser Gly Ala 35 40 45 Pro His Glu Val Gly Trp Lys Tyr GlnAla Val Thr Ala Thr Leu Glu 50 55 60 Glu Lys Arg Lys Glu Lys Ala Glu IleHis Tyr Arg Lys Asn Lys Gln 65 70 75 80 Leu Met Arg Leu Gln Lys Gln AlaGlu Lys Asn Met Lys Lys Lys Ile 85 90 95 Asp Lys Tyr Thr Glu Ser Pro GlyGly Gly Ser Pro Arg Gly Leu Gly 100 105 110 Phe Ile Phe Lys Thr Ile AlaPro Leu Ala Ala Thr Arg Ala Thr Arg 115 120 125 Ile Gly His Pro Gly GlyArg Thr Pro Arg Ala Gly Ser Ser Ala His 130 135 140 Arg Pro Pro Ala LeuSer Ala Arg Ala Pro Val Pro Ala Ala Ser Pro 145 150 155 160 Ala Ala TrpLeu Pro Leu Arg Ser 165 36 354 PRT Homo sapiens 36 Met Lys Ser Leu LeuLeu Leu Val Leu Ile Ser Ile Cys Trp Ala Asp 1 5 10 15 His Leu Ser AspAsn Tyr Thr Leu Asp His Asp Arg Ala Ile His Ile 20 25 30 Gln Ala Glu AsnGly Pro His Leu Leu Val Glu Ala Glu Gln Ala Lys 35 40 45 Val Phe Ser HisArg Gly Gly Asn Val Thr Leu Pro Cys Lys Phe Tyr 50 55 60 Arg Asp Pro ThrAla Phe Gly Ser Gly Ile His Lys Ile Arg Ile Lys 65 70 75 80 Trp Thr LysLeu Thr Ser Asp Tyr Leu Lys Glu Val Asp Val Phe Val 85 90 95 Ser Met GlyTyr His Lys Lys Thr Tyr Gly Gly Tyr Gln Gly Arg Val 100 105 110 Phe LeuLys Gly Gly Ser Asp Ser Asp Ala Ser Leu Val Ile Thr Asp 115 120 125 LeuThr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu Val Ile Glu Gly 130 135 140Leu Glu Asp Asp Thr Val Val Val Ala Leu Asp Leu Gln Gly Val Val 145 150155 160 Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu Asn Phe His Glu165 170 175 Ala Gln Gln Ala Cys Leu Asp Gln Asp Ala Val Ile Ala Ser PheAsp 180 185 190 Gln Leu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp Cys AsnAla Gly 195 200 205 Trp Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr LysPro Arg Glu 210 215 220 Pro Cys Gly Gly Gln Asn Thr Val Pro Gly Val ArgAsn Tyr Gly Phe 225 230 235 240 Trp Asp Lys Asp Lys Ser Arg Tyr Asp ValPhe Cys Phe Thr Ser Asn 245 250 255 Phe Asn Gly Arg Phe Tyr Tyr Leu IleHis Pro Thr Lys Leu Thr Tyr 260 265 270 Asp Glu Ala Val Gln Ala Cys LeuAsn Asp Gly Ala Gln Ile Ala Lys 275 280 285 Val Gly Gln Ile Phe Ala AlaTrp Lys Ile Leu Gly Tyr Asp Arg Cys 290 295 300 Asp Ala Gly Trp Leu AlaAsp Gly Ser Val Arg Tyr Pro Ile Ser Arg 305 310 315 320 Pro Arg Arg ArgCys Ser Pro Thr Glu Ala Ala Val Arg Phe Val Gly 325 330 335 Phe Pro AspLys Lys His Lys Leu Tyr Gly Val Tyr Cys Phe Arg Ala 340 345 350 Tyr Asn37 354 PRT Homo sapiens 37 Met Lys Ser Leu Leu Leu Leu Val Leu Ile SerPhe Cys Trp Ala Asp 1 5 10 15 His His Ser Asp Asn Tyr Thr Val Asp HisAsp Arg Val Ile His Ile 20 25 30 Gln Ala Glu Asn Gly Pro Arg Leu Leu ValGlu Ala Glu Gln Ala Lys 35 40 45 Val Phe Ser Arg Arg Gly Gly Asn Val ThrLeu Pro Cys Lys Phe Tyr 50 55 60 Arg Asp Pro Thr Ala Phe Gly Ser Gly ThrHis Lys Ile Arg Ile Lys 65 70 75 80 Trp Thr Lys Leu Thr Ser Asp Tyr LeuLys Glu Val Asp Val Phe Val 85 90 95 Ser Met Gly Tyr His Lys Lys Thr TyrGly Gly Tyr His Gly Arg Val 100 105 110 Phe Leu Lys Gly Gly Ser Asp AsnAsp Ala Ser Leu Val Ile Thr Asp 115 120 125 Leu Thr Leu Glu Asp Tyr GlyArg Tyr Lys Cys Glu Val Ile Glu Gly 130 135 140 Leu Glu Asp Asp Thr AlaVal Val Ala Leu Asp Leu Gln Gly Val Val 145 150 155 160 Phe Pro Tyr PhePro Arg Leu Gly Arg Tyr Asn Leu Asn Phe His Glu 165 170 175 Ala Gln GlnAla Cys Leu Asp Gln Asp Ala Val Ile Ala Ser Phe Asp 180 185 190 Gln LeuTyr Asp Ala Trp Arg Ser Gly Leu Asp Trp Cys Asn Ala Gly 195 200 205 TrpLeu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr Lys Pro Arg Glu 210 215 220Pro Cys Gly Gly Gln Asn Thr Val Pro Gly Val Arg Asn Tyr Gly Phe 225 230235 240 Trp Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys Phe Thr Ser Asn245 250 255 Phe Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr Lys Leu ThrTyr 260 265 270 Asp Glu Ala Val Gln Ala Cys Leu Asn Asp Gly Ala Gln IleAla Lys 275 280 285 Val Gly Gln Ile Phe Ala Ala Trp Lys Leu Leu Gly TyrAsp Arg Cys 290 295 300 Asp Ala Gly Trp Leu Ala Asp Gly Ser Val Arg TyrPro Ile Ser Arg 305 310 315 320 Pro Arg Arg Arg Cys Ser Pro Ser Glu AlaAla Val Arg Phe Val Gly 325 330 335 Phe Pro Asp Lys Lys His Lys Leu TyrGly Val Tyr Cys Phe Arg Ala 340 345 350 Tyr Asn 38 354 PRT Homo sapiens38 Met Lys Ser Leu Leu Leu Leu Val Leu Ile Ser Ile Cys Trp Ala Asp 1 510 15 His Leu Ser Asp Asn Tyr Thr Leu Asp His Asp Arg Ala Ile His Ile 2025 30 Gln Ala Glu Asn Gly Pro His Leu Leu Val Glu Ala Glu Gln Ala Lys 3540 45 Val Phe Ser His Arg Gly Gly Asn Val Thr Leu Pro Cys Lys Phe Tyr 5055 60 Arg Asp Pro Thr Ala Phe Gly Ser Gly Ile His Lys Ile Arg Ile Lys 6570 75 80 Trp Thr Lys Leu Thr Ser Asp Tyr Leu Lys Glu Val Asp Val Phe Val85 90 95 Ser Met Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr Gln Gly Arg Val100 105 110 Phe Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser Leu Val Ile ThrAsp 115 120 125 Leu Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu Val IleGlu Gly 130 135 140 Leu Glu Asp Asp Thr Val Val Val Ala Leu Asp Leu GlnGly Val Val 145 150 155 160 Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr AsnLeu Asn Phe His Glu 165 170 175 Ala Gln Gln Ala Cys Leu Asp Gln Asp AlaVal Ile Ala Ser Phe Asp 180 185 190 Gln Leu Tyr Asp Ala Trp Arg Gly GlyLeu Asp Trp Cys Asn Ala Gly 195 200 205 Trp Leu Ser Asp Gly Ser Val GlnTyr Pro Ile Thr Lys Pro Arg Glu 210 215 220 Pro Cys Gly Gly Gln Asn ThrVal Pro Gly Val Arg Asn Tyr Gly Phe 225 230 235 240 Trp Asp Lys Asp LysSer Arg Tyr Asp Val Phe Cys Phe Thr Ser Asn 245 250 255 Phe Asn Gly ArgPhe Tyr Tyr Leu Ile His Pro Thr Lys Leu Thr Tyr 260 265 270 Asp Glu AlaVal Gln Ala Cys Leu Asn Asp Gly Ala Gln Ile Ala Lys 275 280 285 Val GlyGln Ile Phe Ala Ala Trp Lys Ile Leu Gly Tyr Asp Arg Cys 290 295 300 AspAla Gly Trp Leu Ala Asp Gly Ser Val Arg Tyr Pro Ile Ser Arg 305 310 315320 Pro Arg Arg Arg Cys Ser Pro Thr Glu Ala Ala Val Arg Phe Val Gly 325330 335 Phe Pro Asp Lys Lys His Lys Leu Tyr Gly Val Tyr Cys Phe Arg Ala340 345 350 Tyr Asn 39 354 PRT Rattus norvegicus 39 Met Arg Ser Leu LeuPhe Leu Val Leu Ile Ser Val Cys Arg Ala Asp 1 5 10 15 His Leu Ser AspSer Tyr Thr Pro Asp Gln Asp Arg Val Ile His Ile 20 25 30 Gln Ala Glu AsnGly Pro Arg Leu Leu Val Glu Ala Glu Gln Ala Lys 35 40 45 Val Phe Ser HisArg Gly Gly Asn Val Thr Leu Pro Cys Lys Phe Tyr 50 55 60 Arg Asp Pro ThrAla Phe Gly Ser Gly Ile His Lys Ile Arg Ile Lys 65 70 75 80 Trp Thr LysLeu Thr Ser Asp Tyr Leu Arg Glu Val Asp Val Phe Val 85 90 95 Ser Met GlyTyr His Lys Lys Thr Tyr Gly Gly Tyr Gln Gly Arg Val 100 105 110 Phe LeuLys Gly Gly Ser Asp Asn Asp Ala Ser Leu Ile Ile Thr Asp 115 120 125 LeuThr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu Val Ile Glu Gly 130 135 140Leu Glu Asp Asp Thr Ala Val Val Ala Leu Glu Leu Gln Gly Val Val 145 150155 160 Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu Asn Phe His Glu165 170 175 Ala Arg Gln Ala Cys Leu Asp Gln Asp Ala Val Ile Ala Ser PheAsp 180 185 190 Gln Leu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp Cys AsnAla Gly 195 200 205 Trp Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr LysPro Arg Glu 210 215 220 Pro Cys Gly Gly Gln Asn Thr Val Pro Gly Val ArgAsn Tyr Gly Phe 225 230 235 240 Trp Asp Lys Asp Lys Ser Arg Tyr Asp ValPhe Cys Phe Thr Ser Asn 245 250 255 Phe Asn Gly Arg Phe Tyr Tyr Leu IleHis Pro Thr Lys Leu Thr Tyr 260 265 270 Asp Glu Ala Val Gln Ala Cys LeuAsn Asp Gly Ala Gln Ile Ala Lys 275 280 285 Val Gly Gln Ile Phe Ala AlaTrp Lys Leu Leu Gly Tyr Asp Arg Cys 290 295 300 Asp Ala Gly Trp Leu AlaAsp Gly Ser Val Arg Tyr Pro Ile Ser Arg 305 310 315 320 Pro Arg Arg ArgCys Ser Pro Thr Glu Ala Ala Val Arg Phe Val Gly 325 330 335 Phe Pro AspLys Lys His Lys Leu Tyr Gly Val Tyr Cys Phe Arg Ala 340 345 350 Tyr Asn40 201 PRT Homo sapiens 40 Lys Ala Glu Asn Gly Pro His Leu Leu Val GluAla Glu Gln Ala Lys 1 5 10 15 Val Phe Ser His Arg Gly Gly Asn Val ThrLeu Pro Cys Lys Phe Tyr 20 25 30 Arg Asp Pro Thr Ala Phe Gly Ser Gly IleHis Lys Ile Arg Ile Lys 35 40 45 Trp Thr Lys Leu Thr Ser Asp Tyr Leu LysGlu Val Asp Val Phe Val 50 55 60 Ser Met Gly Tyr His Lys Lys Thr Tyr GlyGly Tyr Gln Gly Arg Val 65 70 75 80 Phe Leu Lys Gly Gly Ser Asp Ser AspAla Ser Leu Val Ile Thr Asp 85 90 95 Leu Thr Leu Glu Asp Tyr Gly Arg TyrLys Cys Glu Val Ile Glu Gly 100 105 110 Leu Glu Asp Asp Thr Val Val ValAla Leu Asp Leu Gln Gly Val Val 115 120 125 Phe Pro Tyr Phe Pro Arg LeuGly Arg Tyr Asn Leu Asn Phe His Glu 130 135 140 Ala Gln Gln Ala Cys LeuAsp Gln Asp Ala Val Ile Ala Ser Phe Asp 145 150 155 160 Gln Leu Tyr AspAla Trp Arg Gly Gly Leu Asp Trp Cys Asn Ala Gly 165 170 175 Trp Leu SerAsp Gly Ser Val Gln Tyr Pro Ile Thr Lys Pro Arg Glu 180 185 190 Pro CysGly Gly Gln Asn Thr Val Pro 195 200 41 201 PRT Homo sapiens 41 Gln AlaGlu Asn Gly Pro His Leu Leu Val Glu Ala Glu Gln Ala Lys 1 5 10 15 ValPhe Ser His Arg Gly Gly Asn Val Thr Leu Pro Cys Lys Phe Tyr 20 25 30 ArgAsp Pro Thr Ala Phe Gly Ser Gly Ile His Lys Ile Arg Ile Lys 35 40 45 TrpThr Lys Leu Thr Ser Asp Tyr Leu Lys Glu Val Asp Val Phe Val 50 55 60 SerMet Gly Tyr His Lys Lys Thr Tyr Gly Gly Tyr Gln Gly Arg Val 65 70 75 80Phe Leu Lys Gly Gly Ser Asp Ser Asp Ala Ser Leu Val Ile Thr Asp 85 90 95Leu Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu Val Ile Glu Gly 100 105110 Leu Glu Asp Asp Thr Val Val Val Ala Leu Asp Leu Gln Gly Val Val 115120 125 Phe Pro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu Asn Phe His Glu130 135 140 Ala Gln Gln Ala Cys Leu Asp Gln Asp Ala Val Ile Ala Ser PheAsp 145 150 155 160 Gln Leu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp CysAsn Ala Gly 165 170 175 Trp Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile ThrLys Pro Arg Glu 180 185 190 Pro Cys Gly Gly Gln Asn Thr Val Pro 195 20042 354 PRT Homo sapiens 42 Met Lys Ser Leu Leu Leu Leu Val Leu Ile SerIle Cys Trp Ala Asp 1 5 10 15 His Leu Ser Asp Asn Tyr Thr Leu Asp HisAsp Arg Ala Ile His Ile 20 25 30 Gln Ala Glu Asn Gly Pro His Leu Leu ValGlu Ala Glu Gln Ala Lys 35 40 45 Val Phe Ser His Arg Gly Gly Asn Val ThrLeu Pro Cys Lys Phe Tyr 50 55 60 Arg Asp Pro Thr Ala Phe Gly Ser Gly IleHis Lys Ile Arg Ile Lys 65 70 75 80 Trp Thr Lys Leu Thr Ser Asp Tyr LeuLys Glu Val Asp Val Phe Val 85 90 95 Ser Met Gly Tyr His Lys Lys Thr TyrGly Gly Tyr Gln Gly Arg Val 100 105 110 Phe Leu Lys Gly Gly Ser Asp SerAsp Ala Ser Leu Val Ile Thr Asp 115 120 125 Leu Thr Leu Glu Asp Tyr GlyArg Tyr Lys Cys Glu Val Ile Glu Gly 130 135 140 Leu Glu Asp Asp Thr ValVal Val Ala Leu Asp Leu Gln Gly Val Val 145 150 155 160 Phe Pro Tyr PhePro Arg Leu Gly Arg Tyr Asn Leu Asn Phe His Glu 165 170 175 Ala Gln GlnAla Cys Leu Asp Gln Asp Ala Val Ile Ala Ser Phe Asp 180 185 190 Gln LeuTyr Asp Ala Trp Arg Gly Gly Leu Asp Trp Cys Asn Ala Gly 195 200 205 TrpLeu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr Lys Pro Arg Glu 210 215 220Pro Cys Gly Gly Gln Asn Thr Val Pro Gly Val Arg Asn Tyr Gly Phe 225 230235 240 Trp Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys Phe Thr Ser Asn245 250 255 Phe Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr Lys Leu ThrTyr 260 265 270 Asp Glu Ala Val Gln Ala Cys Leu Asn Asp Gly Ala Gln IleAla Lys 275 280 285 Val Gly Gln Ile Phe Ala Ala Trp Lys Ile Leu Gly TyrAsp Arg Cys 290 295 300 Asp Ala Gly Trp Leu Ala Asp Gly Ser Val Arg TyrPro Ile Ser Arg 305 310 315 320 Pro Arg Arg Arg Cys Ser Pro Thr Glu AlaAla Val Arg Phe Val Gly 325 330 335 Phe Pro Asp Lys Lys His Lys Leu TyrGly Val Tyr Cys Phe Arg Ala 340 345 350 Tyr Asn 43 721 PRT Homo sapiens43 Met Leu Glu His Thr Thr Lys Thr Phe Pro Leu Arg Ala Leu His Ile 1 510 15 Val Val Glu Ser Ile Arg Asp His Ser Gly Gln Lys Met Lys Gln Asp 2025 30 Lys Lys Val Asp Leu Leu Val Pro Thr Lys Val Thr Gly Ile Ile Thr 3540 45 Gln Gly Ala Lys Asp Phe Gly His Val Gln Phe Val Gly Ser Tyr Lys 5055 60 Leu Ala Tyr Ser Asn Asp Gly Glu His Trp Thr Val Tyr Gln Asp Glu 6570 75 80 Lys Gln Arg Lys Asp Lys Val Leu Leu Gly Arg Lys Ala Val Val Val85 90 95 Ser Cys Glu Gly Ile Asn Ile Ser Gly Ser Phe Cys Arg Asn Lys Leu100 105 110 Lys Tyr Leu Ala Phe Leu His Lys Arg Met Asn Thr Asn Pro SerArg 115 120 125 Arg Pro Tyr His Phe Gln Val Pro Ser Arg Ile Phe Trp ArgGln Glu 130 135 140 Lys Ala Asp Gly Gly Ser Cys Cys Pro Gln Gly His AlaSer Glu Ala 145 150 155 160 Tyr Lys Lys Val Cys Leu Ser Gly Ala Pro HisGlu Val Gly Trp Lys 165 170 175 Tyr Gln Ala Val Thr Ala Thr Leu Glu GluLys Arg Lys Glu Lys Ala 180 185 190 Glu Ile His Tyr Arg Lys Asn Lys GlnLeu Met Arg Leu Gln Lys Gln 195 200 205 Ala Glu Lys Asn Met Lys Lys LysIle Asp Lys Tyr Thr Glu Ser Pro 210 215 220 Gly Gly Gly Ser Pro Arg GlyLeu Gly Phe Ile Phe Lys Thr Ile Ala 225 230 235 240 Pro Leu Ala Ala ThrArg Ala Thr Arg Ile Gly His Pro Gly Gly Arg 245 250 255 Thr Pro Arg AlaGly Ser Ser Ala His Arg Pro Pro Ala Leu Ser Ala 260 265 270 Arg Ala ProVal Pro Ala Ala Ser Pro Ala Ala Trp Leu Pro Leu Arg 275 280 285 Thr ProTrp Thr Arg Pro Ser Ser Cys Pro Thr Ser Ser Ser Thr Tyr 290 295 300 AspSer Leu Ser Pro Tyr Gly Pro Arg Asn Pro Leu Pro Asn Pro Arg 305 310 315320 His Ser Pro Ser Gly Gly Gly Gly Leu Lys Lys Pro Ala Arg His Cys 325330 335 Gln Gly Gln Lys His Asn Val Leu Ala Arg Gly Lys Pro Gln Arg Lys340 345 350 Pro Lys Ser Glu Asn Asn Ser Trp Tyr Val Glu Asn Gly Arg ProAla 355 360 365 Asp Leu Ala Gly Ser Gly Tyr Cys Gly Ala Leu Trp Lys AlaIle Glu 370 375 380 Ser Leu Glu Glu Gly Leu Gly Gly Lys Gln Lys Asp LysGlu Arg Lys 385 390 395 400 Ala Glu Asn Gly Pro His Leu Leu Val Glu AlaGlu Gln Ala Lys Val 405 410 415 Phe Ser His Arg Gly Gly Asn Val Thr LeuPro Cys Lys Phe Tyr Arg 420 425 430 Asp Pro Thr Ala Phe Gly Ser Gly IleHis Lys Ile Arg Ile Lys Trp 435 440 445 Thr Lys Leu Thr Ser Asp Tyr LeuLys Glu Val Asp Val Phe Val Ser 450 455 460 Met Gly Tyr His Lys Lys ThrTyr Gly Gly Tyr Gln Gly Arg Val Phe 465 470 475 480 Leu Lys Gly Gly SerAsp Ser Asp Ala Ser Leu Val Ile Thr Asp Leu 485 490 495 Thr Leu Glu AspTyr Gly Arg Tyr Lys Cys Glu Val Ile Glu Gly Leu 500 505 510 Glu Asp AspThr Val Val Val Ala Leu Asp Leu Gln Gly Val Val Phe 515 520 525 Pro TyrPhe Pro Arg Leu Gly Arg Tyr Asn Leu Asn Phe His Glu Ala 530 535 540 GlnGln Ala Cys Leu Asp Gln Asp Ala Val Ile Ala Ser Phe Asp Gln 545 550 555560 Leu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp Cys Asn Ala Gly Trp 565570 575 Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr Lys Pro Arg Glu Pro580 585 590 Cys Gly Gly Gln Asn Thr Val Pro Gly Val Arg Asn Tyr Gly PheTrp 595 600 605 Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys Phe Thr SerAsn Phe 610 615 620 Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr Lys LeuThr Tyr Asp 625 630 635 640 Glu Ala Val Gln Ala Cys Leu Asn Asp Gly AlaGln Ile Ala Lys Val 645 650 655 Gly Gln Ile Phe Ala Ala Trp Lys Ile LeuGly Tyr Asp Arg Cys Asp 660 665 670 Ala Gly Trp Leu Ala Asp Gly Ser ValArg Tyr Pro Ile Ser Arg Pro 675 680 685 Arg Arg Arg Cys Ser Pro Thr GluAla Ala Val Arg Phe Val Gly Phe 690 695 700 Pro Asp Lys Lys His Lys LeuTyr Gly Val Tyr Cys Phe Arg Ala Tyr 705 710 715 720 Asn 44 14 PRTTetanus Toxoid 44 Gln Tyr Ile Lys Ala Asn Ser Lys Phe Ile Gly Ile ThrGlu 1 5 10 45 21 PRT Plasmodium falciparum 45 Asp Ile Glu Lys Lys IleAla Lys Met Glu Lys Ala Ser Ser Val Phe 1 5 10 15 Asn Val Val Asn Ser 2046 16 PRT Streptococcus 46 Gly Ala Val Asp Ser Ile Leu Gly Gly Val AlaThr Tyr Gly Ala Ala 1 5 10 15 47 13 PRT Artificial Sequence VARIANT 1,13 Xaa = D-alanine 47 Xaa Lys Xaa Val Ala Ala Trp Thr Leu Lys Ala AlaXaa 1 5 10 48 14 DNA Artificial Sequence Primer 48 ttttgatcaa gctt 14 4942 DNA Artificial Sequence Primer 49 ctaatacgac tcactatagg gctcgagcggccgcccgggc ag 42 50 12 DNA Artificial Sequence Primer 50 gatcctgccc gg12 51 40 DNA Artificial Sequence Primer 51 gtaatacgac tcactatagggcagcgtggt cgcggccgag 40 52 10 DNA Artificial Sequence Primer 52gatcctcggc 10 53 22 DNA Artificial Sequence PCR Primer 53 ctaatacgactcactatagg gc 22 54 22 DNA Artificial Sequence Nested Primer 54tcgagcggcc gcccgggcag ga 22 55 20 DNA Artificial Sequence Nested Primer55 agcgtggtcg cggccgagga 20 56 25 DNA Artificial Sequence Primer 56atatcgccgc gctcgtcgtc gacaa 25 57 26 DNA Artificial Sequence Primer 57agccacacgc agctcattgt agaagg 26 58 24 DNA Artificial Sequence RT-PCRPrimer 58 cccaccaaac tgacctatga tgaa 24 59 25 DNA Artificial SequenceRT-PCR Primer 59 tgtatgctct gaagcagtag acacc 25 60 24 DNA ArtificialSequence Primer 60 gattacaagg atgacgacga taag 24 61 2166 DNA Homosapiens 61 atgttggagc atactactaa gacattcccc ttaagagcac tgcacatagttgtggaaagc 60 attagggacc acagtggcca aaaaatgaag caggataaga aggtggatcttcttgttcca 120 accaaagtga ctggcatcat tacacaagga gctaaagatt ttggtcatgtacagtttgtt 180 ggctcctaca aactggctta cagcaatgat ggagaacact ggactgtataccaggatgaa 240 aagcaaagaa aagataaggt actgctgggc cggaaggcgg tggtcgtaagctgcgaaggc 300 atcaacattt ctggcagttt ctgcagaaac aagttgaagt acctggctttcctccacaag 360 cggatgaaca ccaacccttc tcgacgcccc taccacttcc aggtccccagccgcatcttc 420 tggcgacaag aaaaagcaga tggtggttcc tgctgccctc aaggtcatgcgtctgaagcc 480 tacaagaaag tttgcctatc tggggcgcct cacgaggttg gctggaagtaccaggcagtg 540 acagccaccc tggaggaaaa gaggaaagag aaagccgaga tccactaccggaagaataaa 600 cagctcatga ggctacagaa acaggccgag aagaacatga agaagaaaattgacaaatac 660 acagagagtc caggaggagg cagtccccgt ggcttaggct ttatctttaagacaatagcg 720 ccgctcgccg ccacccgcgc gactcggatc gggcatcccg gcggccgcaccccgcgcgct 780 ggctcatctg cacaccggcc acctgcattg tcggccagag cccccgtcccggcggcttcc 840 ccagcagctt ggctgcccct caggacgccc tggacccgcc catcctcctgccccactagc 900 tcatcgactt acgactccct cagtccctac ggcccacgga accctctccccaacccgcgc 960 cacagcccga gcggcggcgg cggccttaag aagcccgcaa gacactgtcaaggtcaaaag 1020 cacaatgtgc tagccagggg gaaaccccag agaaagccaa aatctgaaaataacagctgg 1080 tatgtagaaa acggcagacc tgctgacttg gcaggctcag gatattgtggtgctctttgg 1140 aaggcaatag agtccttgga ggaaggactt ggaggaaaac aaaaggacaaggaaaggaaa 1200 gcagaaaatg gcccccatct acttgtggaa gcagagcaag ccaaggtgttttcacacaga 1260 ggtggcaatg ttacactgcc atgtaaattt tatcgagacc ctacagcatttggctcagga 1320 atccataaaa tccgaattaa gtggaccaag ctaacttcgg attacctcaaggaagtggat 1380 gtttttgttt ccatgggata ccacaaaaaa acctatggag gctaccagggtagagtgttt 1440 ctgaagggag gcagtgatag tgatgcttct ctggtcatca cagacctcactctggaagat 1500 tatgggagat ataagtgtga ggtgattgaa ggattagaag atgatactgttgtggtagca 1560 ctggacttac aaggtgtggt attcccttac tttccacgac tggggcgctacaatctcaat 1620 tttcacgagg cgcagcaggc gtgtctggac caggatgctg tgatcgcctccttcgaccag 1680 ctgtacgacg cctggcgggg cgggctggac tggtgcaatg ccggctggctcagtgatggc 1740 tctgtgcaat atcccatcac aaagcccaga gagccctgtg gggggcagaacacagtgccc 1800 ggagtcagga actacggatt ttgggataaa gataaaagca gatatgatgttttctgtttt 1860 acatccaatt tcaatggccg tttttactat ctgatccacc ccaccaaactgacctatgat 1920 gaagcggtgc aagcttgtct caatgatggt gctcagattg caaaagtgggccagatattt 1980 gctgcctgga aaattctcgg atatgaccgc tgtgatgcgg gctggttggcggatggcagc 2040 gtccgctacc ccatctctag gccaagaagg cgctgcagtc ctactgaggctgcagtgcgc 2100 ttcgtgggtt tcccagataa aaagcataag ctgtatggtg tctactgcttcagagcatac 2160 aactga 2166 62 1957 DNA Homo sapiens 62 ttaggctgtaattaggggat ttgggaggag aactttcctg gtgacgcttt gcttttcttc 60 tgctcttggtgagaaagtgc ctccttcttc ccaggatcag gacctctgcc atccagcgcc 120 acaaagagacattctgcaca cacactcaca cacacacaca cacacacact ctcacactcg 180 cccagagacaaacttaaggt gaggagaaag agcgctacgt tcacttgatc tccagcttcc 240 aacttaagcagaacttgaga gcatccgaac tcctggattt caggacaagt gaagaagatt 300 ctttgggctataaagatgaa gagtctactt cttctggtgc tgatttcaat ctgctgggct 360 gatcatctttcagacaacta tactctggat catgacagag ctattcacat ccaagcagaa 420 aatggcccccatctacttgt ggaagcagag caagccaagg tgttttcaca cagaggtggc 480 aatgttacactgccatgtaa attttatcga gaccctacag catttggctc aggaatccat 540 aaaatccgaattaagtggac caagctaact tcggattacc tcaaggaagt ggatgttttt 600 gtttccatgggataccacaa aaaaacctat ggaggctacc agggtagagt gtttctgaag 660 ggaggcagtgatagtgatgc ttctctggtc atcacagacc tcactctgga agattatggg 720 agatataagtgtgaggtgat tgaaggatta gaagatgata ctgttgtggt agcactggac 780 ttacaaggtgtggtattccc ttactttcca cgactggggc gctacaatct caattttcac 840 gaggcgcagcaggcgtgtct ggaccaggat gctgtgatcg cctccttcga ccagctgtac 900 gacgcctggcggggcgggct ggactggtgc aatgccggct ggctcagtga tggctctgtg 960 caatatcccatcacaaagcc cagagagccc tgtgggggcc agaacacagt gcccggagtc 1020 aggaactacggattttggga taaagataaa agcagatatg atgttttctg ttttacatcc 1080 aatttcaatggccgttttta ctatctgatc caccccacca aactgaccta tgatgaagcg 1140 gtgcaagcttgtctcaatga tggtgctcag attgcaaaag tgggccagat atttgctgcc 1200 tggaaaattctcggatatga ccgctgtgat gcgggctggt tggcggatgg cagcgtccgc 1260 taccccatctctaggccaag aaggcgctgc agtcctactg aggctgcagt gcgcttcgtg 1320 ggtttcccagataaaaagca taagctgtat ggtgtctact gcttcagagc atacaactga 1380 atgtgcccttagagcgcatc agttttaaag tcattaagaa catgtgaaag gtgttttttt 1440 tttccaatatgaactcatgc aagttaccaa aactgtgata accctttttt acttactgta 1500 aagagtcattttcataagat caattcattg atttgttttt tgtaaagcta tcattcaata 1560 tatattataaattaatataa atttaaggga agctctatgt aaggagactt agagccaaac 1620 tgtttaagctgtatcatccc aacaaagtat cctttcatga acggggcatg caatagctta 1680 agaattgctaggattaaatt aaggaaagta aagctactca gagcaacagg ttccacaagc 1740 acaaactttacacatttgta caattttgaa atgcactaca ataaacaaat tagagcaaca 1800 catttgaaatacaggcttct ttacataaac tgagaggtta tacaaaactc agtttcacaa 1860 gggaacaatctatacctttc taaaagttaa tatttcaagt ctctaatagg cagaatattt 1920 tactctttaaaatcctgcct ttctgaccaa aaaaaaa 1957 63 2166 DNA Homo sapiens 63atgttggagc atactactaa gacattcccc ttaagagcac tgcacatagt tgtggaaagc 60attagggacc acagtggcca aaaaatgaag caggataaga aggtggatct tcttgttcca 120accaaagtga ctggcatcat tacacaagga gctaaagatt ttggtcatgt acagtttgtt 180ggctcctaca aactggctta cagcaatgat ggagaacact ggactgtata ccaggatgaa 240aagcaaagaa aagataaggt actgctgggc cggaaggcgg tggtcgtaag ctgcgaaggc 300atcaacattt ctggcagttt ctgcagaaac aagttgaagt acctggcttt cctccacaag 360cggatgaaca ccaacccttc tcgacgcccc taccacttcc aggtccccag ccgcatcttc 420tggcgacaag aaaaagcaga tggtggttcc tgctgccctc aaggtcatgc gtctgaagcc 480tacaagaaag tttgcctatc tggggcgcct cacgaggttg gctggaagta ccaggcagtg 540acagccaccc tggaggaaaa gaggaaagag aaagccgaga tccactaccg gaagaataaa 600cagctcatga ggctacagaa acaggccgag aagaacatga agaagaaaat tgacaaatac 660acagagagtc caggaggagg cagtccccgt ggcttaggct ttatctttaa gacaatagcg 720ccgctcgccg ccacccgcgc gactcggatc gggcatcccg gcggccgcac cccgcgcgct 780ggctcatctg cacaccggcc acctgcattg tcggccagag cccccgtccc ggcggcttcc 840ccagcagctt ggctgcccct caggacgccc tggacccgcc catcctcctg ccccactagc 900tcatcgactt acgactccct cagtccctac ggcccacgga accctctccc caacccgcgc 960cacagcccga gcggcggcgg cggccttaag aagcccgcaa gacactgtca aggtcaaaag 1020cacaatgtgc tagccagggg gaaaccccag agaaagccaa aatctgaaaa taacagctgg 1080tatgtagaaa acggcagacc tgctgacttg gcaggctcag gatattgtgg tgctctttgg 1140aaggcaatag agtccttgga ggaaggactt ggaggaaaac aaaaggacaa ggaaaggaaa 1200gcagaaaatg gcccccatct acttgtggaa gcagagcaag ccaaggtgtt ttcacacaga 1260ggtggcaatg ttacactgcc atgtaaattt tatcgagacc ctacagcatt tggctcagga 1320atccataaaa tccgaattaa gtggaccaag ctaacttcgg attacctcaa ggaagtggat 1380gtttttgttt ccatgggata ccacaaaaaa acctatggag gctaccaggg tagagtgttt 1440ctgaagggag gcagtgatag tgatgcttct ctggtcatca cagacctcac tctggaagat 1500tatgggagat ataagtgtga ggtgattgaa ggattagaag atgatactgt tgtggtagca 1560ctggacttac aaggtgtggt attcccttac tttccacgac tggggcgcta caatctcaat 1620tttcacgagg cgcagcaggc gtgtctggac caggatgctg tgatcgcctc cttcgaccag 1680ctgtacgacg cctggcgggg cgggctggac tggtgcaatg ccggctggct cagtgatggc 1740tctgtgcaat atcccatcac aaagcccaga gagccctgtg gggggcagaa cacagtgccc 1800ggagtcagga actacggatt ttgggataaa gataaaagca gatatgatgt tttctgtttt 1860acatccaatt tcaatggccg tttttactat ctgatccacc ccaccaaact gacctatgat 1920gaagcggtgc aagcttgtct caatgatggt gctcagattg caaaagtggg ccagatattt 1980gctgcctgga aaattctcgg atatgaccgc tgtgatgcgg gctggttggc ggatggcagc 2040gtccgctacc ccatctctag gccaagaagg cgctgcagtc ctactgaggc tgcagtgcgc 2100ttcgtgggtt tcccagataa aaagcataag ctgtatggtg tctactgctt cagagcatac 2160aactga 2166 64 354 PRT Homo sapiens 64 Met Lys Ser Leu Leu Leu Leu ValLeu Ile Ser Ile Cys Trp Ala Asp 1 5 10 15 His Leu Ser Asp Asn Tyr ThrLeu Asp His Asp Arg Ala Ile His Ile 20 25 30 Gln Ala Glu Asn Gly Pro HisLeu Leu Val Glu Ala Glu Gln Ala Lys 35 40 45 Val Phe Ser His Arg Gly GlyAsn Val Thr Leu Pro Cys Lys Phe Tyr 50 55 60 Arg Asp Pro Thr Ala Phe GlySer Gly Ile His Lys Ile Arg Ile Lys 65 70 75 80 Trp Thr Lys Leu Thr SerAsp Tyr Leu Lys Glu Val Asp Val Phe Val 85 90 95 Ser Met Gly Tyr His LysLys Thr Tyr Gly Gly Tyr Gln Gly Arg Val 100 105 110 Phe Leu Lys Gly GlySer Asp Ser Asp Ala Ser Leu Val Ile Thr Asp 115 120 125 Leu Thr Leu GluAsp Tyr Gly Arg Tyr Lys Cys Glu Val Ile Glu Gly 130 135 140 Leu Glu AspAsp Thr Val Val Val Ala Leu Asp Leu Gln Gly Val Val 145 150 155 160 PhePro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu Asn Phe His Glu 165 170 175Ala Gln Gln Ala Cys Leu Asp Gln Asp Ala Val Ile Ala Ser Phe Asp 180 185190 Gln Leu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp Cys Asn Ala Gly 195200 205 Trp Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr Lys Pro Arg Glu210 215 220 Pro Cys Gly Gly Gln Asn Thr Val Pro Gly Val Arg Asn Tyr GlyPhe 225 230 235 240 Trp Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys PheThr Ser Asn 245 250 255 Phe Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro ThrLys Leu Thr Tyr 260 265 270 Asp Glu Ala Val Gln Ala Cys Leu Asn Asp GlyAla Gln Ile Ala Lys 275 280 285 Val Gly Gln Ile Phe Ala Ala Trp Lys IleLeu Gly Tyr Asp Arg Cys 290 295 300 Asp Ala Gly Trp Leu Ala Asp Gly SerVal Arg Tyr Pro Ile Ser Arg 305 310 315 320 Pro Arg Arg Arg Cys Ser ProThr Glu Ala Ala Val Arg Phe Val Gly 325 330 335 Phe Pro Asp Lys Lys HisLys Leu Tyr Gly Val Tyr Cys Phe Arg Ala 340 345 350 Tyr Asn 65 721 PRTHomo sapiens 65 Met Leu Glu His Thr Thr Lys Thr Phe Pro Leu Arg Ala LeuHis Ile 1 5 10 15 Val Val Glu Ser Ile Arg Asp His Ser Gly Gln Lys MetLys Gln Asp 20 25 30 Lys Lys Val Asp Leu Leu Val Pro Thr Lys Val Thr GlyIle Ile Thr 35 40 45 Gln Gly Ala Lys Asp Phe Gly His Val Gln Phe Val GlySer Tyr Lys 50 55 60 Leu Ala Tyr Ser Asn Asp Gly Glu His Trp Thr Val TyrGln Asp Glu 65 70 75 80 Lys Gln Arg Lys Asp Lys Val Leu Leu Gly Arg LysAla Val Val Val 85 90 95 Ser Cys Glu Gly Ile Asn Ile Ser Gly Ser Phe CysArg Asn Lys Leu 100 105 110 Lys Tyr Leu Ala Phe Leu His Lys Arg Met AsnThr Asn Pro Ser Arg 115 120 125 Arg Pro Tyr His Phe Gln Val Pro Ser ArgIle Phe Trp Arg Gln Glu 130 135 140 Lys Ala Asp Gly Gly Ser Cys Cys ProGln Gly His Ala Ser Glu Ala 145 150 155 160 Tyr Lys Lys Val Cys Leu SerGly Ala Pro His Glu Val Gly Trp Lys 165 170 175 Tyr Gln Ala Val Thr AlaThr Leu Glu Glu Lys Arg Lys Glu Lys Ala 180 185 190 Glu Ile His Tyr ArgLys Asn Lys Gln Leu Met Arg Leu Gln Lys Gln 195 200 205 Ala Glu Lys AsnMet Lys Lys Lys Ile Asp Lys Tyr Thr Glu Ser Pro 210 215 220 Gly Gly GlySer Pro Arg Gly Leu Gly Phe Ile Phe Lys Thr Ile Ala 225 230 235 240 ProLeu Ala Ala Thr Arg Ala Thr Arg Ile Gly His Pro Gly Gly Arg 245 250 255Thr Pro Arg Ala Gly Ser Ser Ala His Arg Pro Pro Ala Leu Ser Ala 260 265270 Arg Ala Pro Val Pro Ala Ala Ser Pro Ala Ala Trp Leu Pro Leu Arg 275280 285 Thr Pro Trp Thr Arg Pro Ser Ser Cys Pro Thr Ser Ser Ser Thr Tyr290 295 300 Asp Ser Leu Ser Pro Tyr Gly Pro Arg Asn Pro Leu Pro Asn ProArg 305 310 315 320 His Ser Pro Ser Gly Gly Gly Gly Leu Lys Lys Pro AlaArg His Cys 325 330 335 Gln Gly Gln Lys His Asn Val Leu Ala Arg Gly LysPro Gln Arg Lys 340 345 350 Pro Lys Ser Glu Asn Asn Ser Trp Tyr Val GluAsn Gly Arg Pro Ala 355 360 365 Asp Leu Ala Gly Ser Gly Tyr Cys Gly AlaLeu Trp Lys Ala Ile Glu 370 375 380 Ser Leu Glu Glu Gly Leu Gly Gly LysGln Lys Asp Lys Glu Arg Lys 385 390 395 400 Ala Glu Asn Gly Pro His LeuLeu Val Glu Ala Glu Gln Ala Lys Val 405 410 415 Phe Ser His Arg Gly GlyAsn Val Thr Leu Pro Cys Lys Phe Tyr Arg 420 425 430 Asp Pro Thr Ala PheGly Ser Gly Ile His Lys Ile Arg Ile Lys Trp 435 440 445 Thr Lys Leu ThrSer Asp Tyr Leu Lys Glu Val Asp Val Phe Val Ser 450 455 460 Met Gly TyrHis Lys Lys Thr Tyr Gly Gly Tyr Gln Gly Arg Val Phe 465 470 475 480 LeuLys Gly Gly Ser Asp Ser Asp Ala Ser Leu Val Ile Thr Asp Leu 485 490 495Thr Leu Glu Asp Tyr Gly Arg Tyr Lys Cys Glu Val Ile Glu Gly Leu 500 505510 Glu Asp Asp Thr Val Val Val Ala Leu Asp Leu Gln Gly Val Val Phe 515520 525 Pro Tyr Phe Pro Arg Leu Gly Arg Tyr Asn Leu Asn Phe His Glu Ala530 535 540 Gln Gln Ala Cys Leu Asp Gln Asp Ala Val Ile Ala Ser Phe AspGln 545 550 555 560 Leu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp Cys AsnAla Gly Trp 565 570 575 Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr LysPro Arg Glu Pro 580 585 590 Cys Gly Gly Gln Asn Thr Val Pro Gly Val ArgAsn Tyr Gly Phe Trp 595 600 605 Asp Lys Asp Lys Ser Arg Tyr Asp Val PheCys Phe Thr Ser Asn Phe 610 615 620 Asn Gly Arg Phe Tyr Tyr Leu Ile HisPro Thr Lys Leu Thr Tyr Asp 625 630 635 640 Glu Ala Val Gln Ala Cys LeuAsn Asp Gly Ala Gln Ile Ala Lys Val 645 650 655 Gly Gln Ile Phe Ala AlaTrp Lys Ile Leu Gly Tyr Asp Arg Cys Asp 660 665 670 Ala Gly Trp Leu AlaAsp Gly Ser Val Arg Tyr Pro Ile Ser Arg Pro 675 680 685 Arg Arg Arg CysSer Pro Thr Glu Ala Ala Val Arg Phe Val Gly Phe 690 695 700 Pro Asp LysLys His Lys Leu Tyr Gly Val Tyr Cys Phe Arg Ala Tyr 705 710 715 720 Asn66 354 PRT Homo sapiens 66 Met Lys Ser Leu Leu Leu Leu Val Leu Ile SerIle Cys Trp Ala Asp 1 5 10 15 His Leu Ser Asp Asn Tyr Thr Leu Asp HisAsp Arg Ala Ile His Ile 20 25 30 Gln Ala Glu Asn Gly Pro His Leu Leu ValGlu Ala Glu Gln Ala Lys 35 40 45 Val Phe Ser His Arg Gly Gly Asn Val ThrLeu Pro Cys Lys Phe Tyr 50 55 60 Arg Asp Pro Thr Ala Phe Gly Ser Gly IleHis Lys Ile Arg Ile Lys 65 70 75 80 Trp Thr Lys Leu Thr Ser Asp Tyr LeuLys Glu Val Asp Val Phe Val 85 90 95 Ser Met Gly Tyr His Lys Lys Thr TyrGly Gly Tyr Gln Gly Arg Val 100 105 110 Phe Leu Lys Gly Gly Ser Asp SerAsp Ala Ser Leu Val Ile Thr Asp 115 120 125 Leu Thr Leu Glu Asp Tyr GlyArg Tyr Lys Cys Glu Val Ile Glu Gly 130 135 140 Leu Glu Asp Asp Thr ValVal Val Ala Leu Asp Leu Gln Gly Val Val 145 150 155 160 Phe Pro Tyr PhePro Arg Leu Gly Arg Tyr Asn Leu Asn Phe His Glu 165 170 175 Ala Gln GlnAla Cys Leu Asp Gln Asp Ala Val Ile Ala Ser Phe Asp 180 185 190 Gln LeuTyr Asp Ala Trp Arg Gly Gly Leu Asp Trp Cys Asn Ala Gly 195 200 205 TrpLeu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr Lys Pro Arg Glu 210 215 220Pro Cys Gly Gly Gln Asn Thr Val Pro Gly Val Arg Asn Tyr Gly Phe 225 230235 240 Trp Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys Phe Thr Ser Asn245 250 255 Phe Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr Lys Leu ThrTyr 260 265 270 Asp Glu Ala Val Gln Ala Cys Leu Asn Asp Gly Ala Gln IleAla Lys 275 280 285 Val Gly Gln Ile Phe Ala Ala Trp Lys Ile Leu Gly TyrAsp Arg Cys 290 295 300 Asp Ala Gly Trp Leu Ala Asp Gly Ser Val Arg TyrPro Ile Ser Arg 305 310 315 320 Pro Arg Arg Arg Cys Ser Pro Thr Glu AlaAla Val Arg Phe Val Gly 325 330 335 Phe Pro Asp Lys Lys His Lys Leu TyrGly Val Tyr Cys Phe Arg Ala 340 345 350 Tyr Asn 67 721 PRT Homo sapiens67 Met Leu Glu His Thr Thr Lys Thr Phe Pro Leu Arg Ala Leu His Ile 1 510 15 Val Val Glu Ser Ile Arg Asp His Ser Gly Gln Lys Met Lys Gln Asp 2025 30 Lys Lys Val Asp Leu Leu Val Pro Thr Lys Val Thr Gly Ile Ile Thr 3540 45 Gln Gly Ala Lys Asp Phe Gly His Val Gln Phe Val Gly Ser Tyr Lys 5055 60 Leu Ala Tyr Ser Asn Asp Gly Glu His Trp Thr Val Tyr Gln Asp Glu 6570 75 80 Lys Gln Arg Lys Asp Lys Val Leu Leu Gly Arg Lys Ala Val Val Val85 90 95 Ser Cys Glu Gly Ile Asn Ile Ser Gly Ser Phe Cys Arg Asn Lys Leu100 105 110 Lys Tyr Leu Ala Phe Leu His Lys Arg Met Asn Thr Asn Pro SerArg 115 120 125 Arg Pro Tyr His Phe Gln Val Pro Ser Arg Ile Phe Trp ArgGln Glu 130 135 140 Lys Ala Asp Gly Gly Ser Cys Cys Pro Gln Gly His AlaSer Glu Ala 145 150 155 160 Tyr Lys Lys Val Cys Leu Ser Gly Ala Pro HisGlu Val Gly Trp Lys 165 170 175 Tyr Gln Ala Val Thr Ala Thr Leu Glu GluLys Arg Lys Glu Lys Ala 180 185 190 Glu Ile His Tyr Arg Lys Asn Lys GlnLeu Met Arg Leu Gln Lys Gln 195 200 205 Ala Glu Lys Asn Met Lys Lys LysIle Asp Lys Tyr Thr Glu Ser Pro 210 215 220 Gly Gly Gly Ser Pro Arg GlyLeu Gly Phe Ile Phe Lys Thr Ile Ala 225 230 235 240 Pro Leu Ala Ala ThrArg Ala Thr Arg Ile Gly His Pro Gly Gly Arg 245 250 255 Thr Pro Arg AlaGly Ser Ser Ala His Arg Pro Pro Ala Leu Ser Ala 260 265 270 Arg Ala ProVal Pro Ala Ala Ser Pro Ala Ala Trp Leu Pro Leu Arg 275 280 285 Thr ProTrp Thr Arg Pro Ser Ser Cys Pro Thr Ser Ser Ser Thr Tyr 290 295 300 AspSer Leu Ser Pro Tyr Gly Pro Arg Asn Pro Leu Pro Asn Pro Arg 305 310 315320 His Ser Pro Ser Gly Gly Gly Gly Leu Lys Lys Pro Ala Arg His Cys 325330 335 Gln Gly Gln Lys His Asn Val Leu Ala Arg Gly Lys Pro Gln Arg Lys340 345 350 Pro Lys Ser Glu Asn Asn Ser Trp Tyr Val Glu Asn Gly Arg ProAla 355 360 365 Asp Leu Ala Gly Ser Gly Tyr Cys Gly Ala Leu Trp Lys AlaIle Glu 370 375 380 Ser Leu Glu Glu Gly Leu Gly Gly Lys Gln Lys Asp LysGlu Arg Lys 385 390 395 400 Ala Glu Asn Gly Pro His Leu Leu Val Glu AlaGlu Gln Ala Lys Val 405 410 415 Phe Ser His Arg Gly Gly Asn Val Thr LeuPro Cys Lys Phe Tyr Arg 420 425 430 Asp Pro Thr Ala Phe Gly Ser Gly IleHis Lys Ile Arg Ile Lys Trp 435 440 445 Thr Lys Leu Thr Ser Asp Tyr LeuLys Glu Val Asp Val Phe Val Ser 450 455 460 Met Gly Tyr His Lys Lys ThrTyr Gly Gly Tyr Gln Gly Arg Val Phe 465 470 475 480 Leu Lys Gly Gly SerAsp Ser Asp Ala Ser Leu Val Ile Thr Asp Leu 485 490 495 Thr Leu Glu AspTyr Gly Arg Tyr Lys Cys Glu Val Ile Glu Gly Leu 500 505 510 Glu Asp AspThr Val Val Val Ala Leu Asp Leu Gln Gly Val Val Phe 515 520 525 Pro TyrPhe Pro Arg Leu Gly Arg Tyr Asn Leu Asn Phe His Glu Ala 530 535 540 GlnGln Ala Cys Leu Asp Gln Asp Ala Val Ile Ala Ser Phe Asp Gln 545 550 555560 Leu Tyr Asp Ala Trp Arg Gly Gly Leu Asp Trp Cys Asn Ala Gly Trp 565570 575 Leu Ser Asp Gly Ser Val Gln Tyr Pro Ile Thr Lys Pro Arg Glu Pro580 585 590 Cys Gly Gly Gln Asn Thr Val Pro Gly Val Arg Asn Tyr Gly PheTrp 595 600 605 Asp Lys Asp Lys Ser Arg Tyr Asp Val Phe Cys Phe Thr SerAsn Phe 610 615 620 Asn Gly Arg Phe Tyr Tyr Leu Ile His Pro Thr Lys LeuThr Tyr Asp 625 630 635 640 Glu Ala Val Gln Ala Cys Leu Asn Asp Gly AlaGln Ile Ala Lys Val 645 650 655 Gly Gln Ile Phe Ala Ala Trp Lys Ile LeuGly Tyr Asp Arg Cys Asp 660 665 670 Ala Gly Trp Leu Ala Asp Gly Ser ValArg Tyr Pro Ile Ser Arg Pro 675 680 685 Arg Arg Arg Cys Ser Pro Thr GluAla Ala Val Arg Phe Val Gly Phe 690 695 700 Pro Asp Lys Lys His Lys LeuTyr Gly Val Tyr Cys Phe Arg Ala Tyr 705 710 715 720 Asn

1. A composition comprising: a substance that a) modulates the status of a protein of FIG. 2 (SEQ ID NOS:______), or b) a molecule that is modulated by a protein of FIG. 2, whereby the status of a cell that expresses a protein of FIG. 2 is modulated.
 2. A composition of claim 1, further comprising a physiologically acceptable carrier.
 3. A pharmaceutical composition that comprises the composition of claim 1 in a human unit dose form.
 4. A composition of claim 1 wherein the substance comprises an antibody or fragment thereof that specifically binds to a protein that is related to a protein of FIG.
 2. 5. An antibody or fragment thereof of claim 4, which is monoclonal.
 6. An antibody of claim 4, which is a human antibody, a humanized antibody or a chimeric antibody.
 7. A non-human transgenic animal that produces an antibody of claim
 4. 8. A hybridoma that produces an antibody of claim
 5. 9. A method of delivering a cytotoxic agent or a diagnostic agent to a cell that expresses a protein of FIG. 2 (SEQ ID NOS: ______), said method comprising: providing the cytotoxic agent or the diagnostic agent conjugated to an antibody or fragment thereof of claim 4; and, exposing the cell to the antibody-agent or fragment-agent conjugate.
 10. A composition of claim 1 wherein the substance comprises a polynucleotide that encodes an antibody or fragment thereof, either of which immunospecifically bind to a protein of FIG.
 2. 11. A composition of claim 1 wherein the substance comprises a protein related to a protein of FIG.
 2. 12. A protein of claim 11 that is at least 90% homologous to an entire amino acid sequence shown in FIG. 2 (SEQ ID NOS: ______).
 13. A composition of claim 1 wherein the substance comprises: a) a peptide of eight, nine, ten, or eleven contiguous amino acids of a protein of FIG. 2; b) a peptide of Tables V to XVIII (SEQ ID NOS: ______); c) a peptide of Tables XXII to XLVII (SEQ ID NOS: ______); or, d) a peptide of Tables XLVIII to LI (SEQ ID NOS: ______).
 14. A composition of claim 1 wherein the substance comprises a CTL polypeptide or an analog thereof, from the amino acid sequence of a protein of FIG. 2 (SEQ ID NOS: ______).
 15. A composition of claim 14 further limited by a proviso that the epitope is not an entire amino acid sequence of FIG. 2 (SEQ ID NOS:).
 16. A composition of claim 14 wherein the substance comprises a CTL polypeptide set forth in Tables V to XVIII (SEQ ID NOS: ______).
 17. A composition of claim 16 further limited by a proviso that the polypeptide is not an entire amino acid sequence of a protein of FIG. 2 (SEQ ID NOS: ______).
 18. A composition of claim 1 wherein the substance comprises an antibody polypeptide epitope from an amino acid sequence of FIG. 2 (SEQ ID NOS: ______).
 19. A composition of claim 18 further limited by a proviso that the epitope is not an entire amino acid sequence of FIG. 2 (SEQ ID NOS: ______).
 20. A composition of claim 18 wherein the antibody epitope comprises a peptide region of at least 5 amino acids of FIG. 2 (SEQ ID NOS: ______) in any whole number increment up to the end of said peptide, wherein the epitope comprises an amino acid position selected from: a) an amino acid position having a value greater than 0.5 in the Hydrophilicity profile of FIG. 5, b) an amino acid position having a value less than 0.5 in the Hydropathicity profile of FIG. 6; c) an amino acid position having a value greater than 0.5 in the Percent Accessible Residues profile of FIG. 7; d) an amino acid position having a value greater than 0.5 in the Average Flexibility profile of FIG. 8; e) an amino acid position having a value greater than 0.5 in the Beta-turn profile of FIG. 9; f) a combination of at least two of a) through e); g) a combination of at least three of a) through e); h) a combination of at least four of a) through e); or i) a combination of five of a) through e).
 21. A composition of claim 20 further limited by a proviso that the epitope is not an entire amino acid sequence of FIG. 2 (SEQ ID NOS: ______).
 22. A polynucleotide that encodes a protein of claim
 11. 23. A polynucleotide of claim 22 that comprises a nucleic acid molecule set forth in FIG.
 2. 24. A polynucleotide of claim 22 further limited by a proviso that the encoded protein is not an entire amino acid sequence of FIG. 2 (SEQ ID NOS: ______).
 25. A polynucleotide of claim 22 wherein T is substituted with U.
 26. A composition of claim 1 wherein the substance comprises a polynucleotide that comprises a coding sequence of a nucleic acid sequence of FIG. 2 (SEQ ID NOS: ______).
 27. A polynucleotide of claim 22 that further comprises an additional nucleotide sequence that encodes an additional protein of claim
 11. 28. A composition comprising a polynucleotide that is fully complementary to a polynucleotide of claim
 22. 29. A composition comprising a polynucleotide that is fully complementary to a polynucleotide of claim
 25. 30. A composition comprising a polynucleotide that is fully complementary to a polynucleotide of claim
 27. 31. A composition of claim 1 wherein the substance comprises a) a ribozyme that cleaves a polynucleotide having a 151P3D4 coding sequence, or b) a nucleic acid molecule that encodes the ribozyme; and, a physiologically acceptable carrier.
 32. A composition of claim 1 wherein the substance comprises human T cells, wherein said T cells specifically recognize a 151P3D4 peptide subsequence in the context of a particular HLA molecule.
 33. A method of inhibiting growth of cancer cells that express a protein of FIG. 2, the method comprising: administering to the cells the composition of claim
 1. 34. A method of claim 33 of inhibiting growth of cancer cells that express a protein of FIG. 2, the method comprising steps of: administering to said cells an antibody or fragment thereof, either of which specifically bind to a 151P3D4-related protein.
 35. A method of claim 33 of inhibiting growth of cancer cells that express a protein of FIG. 2, the method comprising steps of: administering to said cells a 151P3D4-related protein.
 36. A method of claim 33 of inhibiting growth of cancer cells that express a protein of FIG. 2, the method comprising steps of: administering to said cells a polynucleotide comprising a coding sequence for a 151P3D4-related protein or comprising a polynucleotide complementary to a coding sequence for a 151P3D4-related protein.
 37. A method of claim 33 of inhibiting growth of cancer cells that express a protein of FIG. 2, the method comprising steps of: administering to said cells a ribozyme that cleaves a polynucleotide that encodes a protein of FIG.
 2. 38. A method of claim 33 of inhibiting growth of cancer cells that express a protein of FIG. 2 and a particular HLA molecule, the method comprising steps of: administering human T cells to said cancer cells, wherein said T cells specifically recognize a peptide subsequence of a protein of FIG. 2 while the subsequence is in the context of the particular HLA molecule.
 39. A method of claim 33, the method comprising steps of: administering a vector that delivers a nucleotide that encodes a single chain monoclonal antibody, whereby the encoded single chain antibody is expressed intracellularly within cancer cells that express a protein of FIG.
 2. 40. A method of generating a mammalian immune response directed to a protein of FIG. 2, the method comprising: exposing cells of the mammal's immune system to a portion of a) a 151P3D4-related protein and/or b) a nucleotide sequence that encodes said protein, whereby an immune response is generated to said protein.
 41. A method of generating an immune response of claim 40, said method comprising: providing a 151P3D4-related protein that comprises at least one T cell or at least one B cell epitope; and, contacting the epitope with a mammalian immune system T cell or B cell respectively, whereby the T cell or B cell is activated.
 42. A method of claim 41 wherein the immune system cell is a B cell, whereby the induced B cell generates antibodies that specifically bind to the 151P3D4-related protein.
 43. A method of claim 41 wherein the immune system cell is a T cell that is a cytotoxic T cell (CTL), whereby the activated CTL kills an autologous cell that expresses the 151P3D4-related protein.
 44. A method of claim 41 wherein the immune system cell is a T cell that is a helper T cell (HTL), whereby the activated HTL secretes cytokines that facilitate the cytotoxic activity of a cytotoxic T cell (CTL) or the antibody-producing activity of a B cell.
 45. A method for detecting, in a sample, the presence of a 151P3D4-related protein or a 151P3D4-related polynucleotide, comprising steps of: contacting the sample with a substance of claim 1 that specifically binds to the 151P3D4-related protein or to the 151P3D4-related polynucleotide, respectively; and, determining that there is a complex of the substance with the 151P3D4-related protein or the substance with the 151P3D4-related polynucleotide, respectively.
 46. A method of claim 45 for detecting the presence of a 151P3D4-related protein in a sample comprising steps of: contacting the sample with an antibody or fragment thereof either of which specifically bind to the 151P3D4-related protein; and, determining that there is a complex of the antibody or fragment thereof and the 151P3D4-related protein.
 47. A method of claim 45 further comprising a step of: taking the sample from a patient who has or who is suspected of having cancer.
 48. A method of claim 45 for detecting the presence of a protein of FIG. 2 mRNA in a sample comprising: producing cDNA from the sample by reverse transcription using at least one primer; amplifying the cDNA so produced using 151P3D4 polynucleotides as sense and antisense primers, wherein the 151P3D4 polynucleotides used as the sense and antisense primers serve to amplify a 151P3D4 cDNA; and, detecting the presence of the amplified 151P3D4 cDNA.
 49. A method of claim 45 for monitoring one or more 151P3D4 gene products in a biological sample from a patient who has or who is suspected of having cancer, the method comprising: determining the status of one or more 151P3D4 gene products expressed by cells in a tissue sample from an individual; comparing the status so determined to the status of one or more 151P3D4 gene products in a corresponding normal sample; and, identifying the presence of one or more aberrant gene products of 151P3D4 in the sample relative to the normal sample.
 50. The method of claim 49 further comprising a step of determining if there are one or more elevated gene products of a 151P3D4 mRNA or a 151P3D4 protein, whereby the presence of one or more elevated gene products in the test sample relative to the normal tissue sample indicates the presence or status of a cancer.
 51. A method of claim 50 wherein the cancer occurs in a tissue set forth in Table I. 